Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PubMed

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial.

PubMed

Swaminath, Anand; Wierzbicki, Marcin; Parpia, Sameer; Wright, James R; Tsakiridis, Theodoros K; Okawara, Gordon S; Kundapur, Vijayananda; Bujold, Alexis; Ahmed, Naseer; Hirmiz, Khalid; Kurien, Elizabeth; Filion, Edith; Gabos, Zsolt; Faria, Sergio; Louie, Alexander V; Owen, Timothy; Wai, Elaine; Ramchandar, Kevin; Chan, Elisa K; Julian, Jim; Cline, Kathryn; Whelan, Timothy J

2017-03-01

We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.5% with SBRT. With 85% power to detect a difference of this magnitude (hazard ratio = 0.46), a 2-sided α = 0.05 and a 2:1 randomization, we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary outcomes include overall survival, disease-free survival, toxicity, radiation-related treatment death, quality of life, and cost-effectiveness. A robust radiation therapy quality assurance program has been established to assure consistent and high quality SBRT and CRT delivery. Despite widespread interest and adoption of SBRT, there still remains a concern regarding long-term control and risks of toxicity (particularly in patients with centrally located lesions). The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a medically inoperable population, and the results of this trial will attempt to prove that the benefits of SBRT outweigh the potential risks. Copyright © 2016 Elsevier Inc. All rights reserved.

Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.

PubMed

Louis, Scott G; Van, Philbert Y; Riha, Gordon M; Barton, Jeffrey S; Kunio, Nicholas R; Underwood, Samantha J; Differding, Jerome A; Rick, Elizabeth; Ginzburg, Enrique; Schreiber, Martin A

2014-04-01

The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. Therapeutic study, level III.

Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial.

PubMed

Dey, Mahua; Stadnik, Agnieszka; Riad, Fady; Zhang, Lingjiao; McBee, Nichol; Kase, Carlos; Carhuapoma, J Ricardo; Ram, Malathi; Lane, Karen; Ostapkovich, Noeleen; Aldrich, Francois; Aldrich, Charlene; Jallo, Jack; Butcher, Ken; Snider, Ryan; Hanley, Daniel; Ziai, Wendy; Awad, Issam A

2015-03-01

Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication. To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature. Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software. Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis. Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to >60 trial sites.

A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).

PubMed

Bellmunt, J; Kerst, J M; Vázquez, F; Morales-Barrera, R; Grande, E; Medina, A; González Graguera, M B; Rubio, G; Anido, U; Fernández Calvo, O; González-Billalabeitia, E; Van den Eertwegh, A J M; Pujol, E; Perez-Gracia, J L; González Larriba, J L; Collado, R; Los, M; Maciá, S; De Wit, R

2017-07-01

Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. NCT01830231. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Influence of work clothing on physiological responses and performance during treadmill exercise and the Wildland Firefighter Pack Test.

PubMed

Phillips, Devin B; Ehnes, Cameron M; Welch, Bradley G; Lee, Lauren N; Simin, Irina; Petersen, Stewart R

2018-04-01

This study investigated physiological responses and performance during three separate exercise challenges (Parts I, II, and III) with wildland firefighting work clothing ensemble (boots and coveralls) and a 20.4 kg backpack in four conditions: U-EX (no pack, exercise clothing); L-EX (pack, exercise clothing); U-W (no pack, work clothing); and, L-W (pack and work clothing). Part I consisted of randomly-ordered graded exercise tests, on separate days, in U-EX, L-EX and L-W conditions. Part II consisted of randomly-ordered bouts of sub-maximal treadmill exercise in the four conditions. In Part III, subjects completed, in random-order on separate days, 4.83 km Pack Tests in L-EX or L-W conditions. In Part I, peak oxygen uptake was reduced (p < .05) in L-W. In Part II, mass-specific oxygen uptake was significantly higher in both work clothing conditions. In Part III, Pack Test time was slower (p < .05) in L-W. These results demonstrate the negative impact of work clothing and load carriage on physiological responses to exercise and performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

PubMed Central

2012-01-01

Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. Conclusions The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Trial registration Phase I/II trial, NCT00598130 PMID:23137020

Accurate determination of interfacial protein secondary structure by combining interfacial-sensitive amide I and amide III spectral signals.

PubMed

Ye, Shuji; Li, Hongchun; Yang, Weilai; Luo, Yi

2014-01-29

Accurate determination of protein structures at the interface is essential to understand the nature of interfacial protein interactions, but it can only be done with a few, very limited experimental methods. Here, we demonstrate for the first time that sum frequency generation vibrational spectroscopy can unambiguously differentiate the interfacial protein secondary structures by combining surface-sensitive amide I and amide III spectral signals. This combination offers a powerful tool to directly distinguish random-coil (disordered) and α-helical structures in proteins. From a systematic study on the interactions between several antimicrobial peptides (including LKα14, mastoparan X, cecropin P1, melittin, and pardaxin) and lipid bilayers, it is found that the spectral profiles of the random-coil and α-helical structures are well separated in the amide III spectra, appearing below and above 1260 cm(-1), respectively. For the peptides with a straight backbone chain, the strength ratio for the peaks of the random-coil and α-helical structures shows a distinct linear relationship with the fraction of the disordered structure deduced from independent NMR experiments reported in the literature. It is revealed that increasing the fraction of negatively charged lipids can induce a conformational change of pardaxin from random-coil to α-helical structures. This experimental protocol can be employed for determining the interfacial protein secondary structures and dynamics in situ and in real time without extraneous labels.

Interplanetary Type III Bursts and Electron Density Fluctuations in the Solar Wind

NASA Astrophysics Data System (ADS)

Krupar, V.; Maksimovic, M.; Kontar, E. P.; Zaslavsky, A.; Santolik, O.; Soucek, J.; Kruparova, O.; Eastwood, J. P.; Szabo, A.

2018-04-01

Type III bursts are generated by fast electron beams originated from magnetic reconnection sites of solar flares. As propagation of radio waves in the interplanetary medium is strongly affected by random electron density fluctuations, type III bursts provide us with a unique diagnostic tool for solar wind remote plasma measurements. Here, we performed a statistical survey of 152 simple and isolated type III bursts observed by the twin-spacecraft Solar TErrestrial RElations Observatory mission. We investigated their time–frequency profiles in order to retrieve decay times as a function of frequency. Next, we performed Monte Carlo simulations to study the role of scattering due to random electron density fluctuations on time–frequency profiles of radio emissions generated in the interplanetary medium. For simplification, we assumed the presence of isotropic electron density fluctuations described by a power law with the Kolmogorov spectral index. Decay times obtained from observations and simulations were compared. We found that the characteristic exponential decay profile of type III bursts can be explained by the scattering of the fundamental component between the source and the observer despite restrictive assumptions included in the Monte Carlo simulation algorithm. Our results suggest that relative electron density fluctuations < δ {n}{{e}}> /{n}{{e}} in the solar wind are 0.06–0.07 over wide range of heliospheric distances.

Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial.

PubMed

Shehata, Nadine; Whitlock, Richard; Fergusson, Dean A; Thorpe, Kevin E; MacAdams, Charlie; Grocott, Hilary P; Rubens, Fraser; Fremes, Stephen; Lellouche, Francois; Bagshaw, Sean; Royse, Alistair; Rosseel, Peter M; Hare, Greg; Medicis, Etienne De; Hudson, Christopher; Belley-Cote, Emilie; Bainbridge, Daniel; Kent, Blaine; Shaw, Andrew; Byrne, Kelly; Syed, Summer; Royse, Colin F; McGuiness, Shay; Hall, Judith; Mazer, C David

2018-02-01

To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity. Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898). Eligible patients were randomized prior to surgery in a 1:1 ratio. Potential participants were 18 years or older undergoing planned cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more. Five thousand patients; those allocated to a restrictive transfusion group received a red blood cell (RBC) transfusion if the hemoglobin concentration (Hb) was less than 7.5 g/dL intraoperatively and/or postoperatively. Patients allocated to a liberal transfusion strategy received RBC transfusion if the Hb was less than 9.5 g/dL intraoperatively or postoperatively in the intensive care unit or less than 8.5 g/dL on the ward. The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or new onset renal dysfunction requiring dialysis at hospital discharge or day 28, whichever comes first. The primary outcome was analyzed as a per-protocol analysis. The trial monitored adherence closely as adherence to the transfusion triggers is important in ensuring that measured outcomes reflect the transfusion strategy. By randomizing prior to surgery, the TRICS III trial captured the most acute reduction in hemoglobin during cardiopulmonary bypass. Copyright © 2018. Published by Elsevier Inc.

Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane.

PubMed

Kaufman, Peter A; Awada, Ahmad; Twelves, Chris; Yelle, Louise; Perez, Edith A; Velikova, Galina; Olivo, Martin S; He, Yi; Dutcus, Corina E; Cortes, Javier

2015-02-20

This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS.

A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO).

PubMed

Sehouli, Jalid; Tomè, Oliver; Dimitrova, Desislava; Camara, Oumar; Runnebaum, Ingo Bernhard; Tessen, Hans Werner; Rautenberg, Beate; Chekerov, Radoslav; Muallem, Mustafa Zelal; Lux, Michael Patrick; Trarbach, Tanja; Gitsch, Gerald

2017-03-01

In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC. Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m 2 d1 q4w or treosulfan p.o. 600 mg/m 2 d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life. 250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred. Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.

Effect of Herbal and Fluoride Mouth Rinses on Streptococcus mutans and Dental Caries among 12–15-Year-Old School Children: A Randomized Controlled Trial

PubMed Central

Shenoy Panchmal, Ganesh; Kumar, Vijaya; Jodalli, Praveen S.; Sonde, Laxminarayan

2017-01-01

To assess and compare the effect of herbal and fluoride mouth rinses on Streptococcus mutans count and glucan synthesis by Streptococcus mutans and dental caries, a parallel group placebo controlled randomized trial was conducted among 240 schoolchildren (12–15 years old). Participants were randomly divided and allocated into Group I (0.2% fluoride group), Group II (herbal group), and Group III (placebo group). All received 10 ml of respective mouth rinses every fortnight for a period of one year. Intergroup and intragroup comparison were done for Streptococcus mutans count and glucan synthesis by Streptococcus mutans and dental caries. Streptococcus mutans count showed a statistically significant difference between Group I and Group III (p = 0.035) and also between Group II and Group III (p = 0.039). Glucan concentration levels showed a statistically significant difference (p = 0.024) between Group II and Group III at 12th month. Mean DMF scores showed no statistical difference between the three groups (p = 0.139). No difference in the level of significance was seen in the intention-to-treat and per-protocol analysis. The present study showed that both herbal and fluoride mouth rinses, when used fortnightly, were equally effective and could be recommended for use in school-based health education program to control dental caries. Trial registration number is CTRI/2015/08/006070. PMID:28352285

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III-rationale, trial design and baseline data.

PubMed

2017-12-01

Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

A prospective randomized trial comparing Foley catheter, oxytocin, and combination Foley catheter-oxytocin for labour induction with unfavourable cervix.

PubMed

El Khouly, Nabih I

2017-04-01

The purpose of this study was to evaluate the effectiveness and safety of transcervical Foley catheter with and without oxytocin versus oxytocin alone for labour induction with unfavourable cervix. This trial enrolled 108 women with singleton pregnancies presented for labour induction with unfavourable cervix. Patients were randomly assigned to receive Foley catheter alone (I), Foley catheter plus oxytocin (II) or oxytocin alone (III). Outcomes were analysed in terms of success of induction, induction delivery interval, route of delivery, dose and duration of oxytocin, and complications. Successful normal vaginal delivery was more common in group I (p = .02) compared to group III. Induction delivery time was statistically shorter in group II and group III (p < .001). Patients in group I required significantly less oxytocin dose and duration (p < .001). This led to our conclusion that induction of labour with Foley catheter without oxytocin increases success rate of normal vaginal delivery; however, it has a longer induction delivery interval with similar complications.

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A.

PubMed

Welzel, Grit; Boch, Angela; Sperk, Elena; Hofmann, Frank; Kraus-Tiefenbacher, Uta; Gerhardt, Axel; Suetterlin, Marc; Wenz, Frederik

2013-01-07

Intraoperative radiotherapy (IORT) is a new treatment approach for early stage breast cancer. This study reports on the effects of IORT on radiation-related quality of life (QoL) parameters. Two hundred and thirty women with stage I-III breast cancer (age, 31 to 84 years) were entered into the study. A single-center subgroup of 87 women from the two arms of the randomized phase III trial TARGIT-A (TARGeted Intra-operative radioTherapy versus whole breast radiotherapy for breast cancer) was analyzed. Furthermore, results were compared to non-randomized control groups: n = 90 receiving IORT as a tumor bed boost followed by external beam whole breast radiotherapy (EBRT) outside of TARGIT-A (IORT-boost), and n = 53 treated with EBRT followed by an external-beam boost (EBRT-boost). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 (QLQ-C30) and BR23 (QLQ-BR23). The mean follow-up period in the TARGIT-A groups was 32 versus 39 months in the non-randomized control groups. Patients receiving IORT alone reported less general pain (21.3 points), breast (7.0 points) and arm (15.1 points) symptoms, and better role functioning (78.7 points) as patients receiving EBRT (40.9; 19.0; 32.8; and 60.5 points, respectively, P < 0.01). Patients receiving IORT alone also had fewer breast symptoms than TARGIT-A patients receiving IORT followed by EBRT for high risk features on final pathology (IORT-EBRT; 7.0 versus 29.7 points, P < 0.01). There were no significant differences between TARGIT-A patients receiving IORT-EBRT compared to non-randomized IORT-boost or EBRT-boost patients and patients receiving EBRT without a boost. In the randomized setting, important radiation-related QoL parameters after IORT were superior to EBRT. Non-randomized comparisons showed equivalent parameters in the IORT-EBRT group and the control groups.

Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins.

PubMed

Furtado, Jeremy D; Wedel, Mark K; Sacks, Frank M

2012-04-01

Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III-containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38-42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III-containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors.

Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study.

PubMed

Pivonello, Rosario; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Trovato, Andrew; Hughes, Gareth; Salgado, Luiz R; Lacroix, André; Schopohl, Jochen; Biller, Beverly M K

2014-09-01

Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. Phase III study with double-blind randomization of two pasireotide doses. Patients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1·5× upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 μg bid). At month 3, patients with UFC ≤2 × ULN and not exceeding the baseline value continued their randomized dose; all others received 300 μg bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200 μg bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control. Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low-density lipoprotein (LDL)-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72·8% of patients. In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased. © 2014 John Wiley & Sons Ltd.

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

Effect of oral cranberry extract (standardized proanthocyanidin-A) in patients with recurrent UTI by pathogenic E. coli: a randomized placebo-controlled clinical research study.

PubMed

Singh, Iqbal; Gautam, Lokesh Kumar; Kaur, Iqbal R

2016-09-01

To evaluate the effect of cranberry extract (PAC-A ~ proanthocyanidin-A) on the in vitro bacterial properties of uropathogenic (E. coli) and its efficacy/tolerability in patients with subclinical or uncomplicated recurrent UTI (r-UTI). After obtaining clearance from the ethics committee and administering a written informed consent, 72 patients with r-UTI were enrolled as per protocol (November 2011 to March 2013) in this prospective study, to randomly receive (PAC-A: group I, 36) or (placebo: group II, 36), for 12 weeks. Any change/reduction in the incidence of r-UTI at 12 weeks was construed to be the primary endpoint of this study. After 12 weeks, bacterial adhesion scoring decreased (0.28)/(2.14) in group I/II (p < 0.001); 32/36 (88.8 %) and 2/36 (5.5 %) in groups I and II, respectively, turned MRHA negative (p < 0.001); biofilm (p < 0.01) and bacterial growth (p < 0.001) decreased in group I; microscopic pyuria score was 0.36/2.0 in group I/II (p < 0.001); r-UTI decreased to 33.33 versus 88.89 % in group I/II (p < 0.001); mean subjective dysuria score was 0.19 versus 1.47 in group I/II (p < 0.001), while mean urine pH was 5.88 versus 6.30 in group I/II (p < 0.001). No in vitro antibacterial activity of cranberry could be demonstrated, and no adverse events were noted. The overall efficacy and tolerability of standardized cranberry extract containing (PAC-A) as a food supplement were superior to placebo in terms of reduced bacterial adhesion; bacterial MRHA negativity; urine pH reduction; and in preventing r-UTI (dysuria, bacteriuria and pyuria). Larger randomized controlled trials are needed to elucidate the precise role, exact dose and optimal duration of PAC-A therapy in patients at risk of r-UTI.

PPH versus THD: a comparison of two techniques for III and IV degree haemorrhoids. Personal experience.

PubMed

Verre, L; Rossi, R; Gaggelli, I; Di Bella, C; Tirone, A; Piccolomini, A

2013-12-01

The aim of our study was to evaluate, through prospective randomized study, the outcome and the immediate and late complications of the two types of surgery most widely used for degree III-IV haemorrhoids. A total of 122 patients with degree III and IV hemorrhoids were elected for surgical intervention and, randomly, underwent surgery for PPH or THD. We assessed the most common immediate postoperative complications. The patients have been followed for three months with a mean follow-up at 1 month and 3 months after surgery. Parameters taken into consideration were: bleeding, pain at rest and after evacuation, soiling, constipation and tenesmus. Five patients in PPH group (7.9%) had a major postoperative bleeding, whereas no such episode occurred in THD group (P=ns). In percentage terms, VAS score was lower in THD group than in PPH group, although the difference was not statistically significant. Finally parameters values observed, during the follow-up, proved to be lower for THD group compared to PPH group. PPH and THD are two surgical treatments for degree III and IV haemorrhoids with low perioperative complications and good results in the short term. However, our experience shows that better results in terms of pain and fewer postoperative complications are obtained after THD surgery, such surgery is less invasive and more adaptable to the needs of day surgery.

Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

PubMed

Ribas, Antoni; Kefford, Richard; Marshall, Margaret A; Punt, Cornelis J A; Haanen, John B; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A; Dreno, Brigitte; Nathan, Paul D; Mackiewicz, Jacek; Kirkwood, John M; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

2013-02-10

In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.

Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial.

PubMed

Tomusiak, Anna; Strus, Magdalena; Heczko, Piotr B; Adamski, Paweł; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena

2015-01-01

The main objective of this study was to evaluate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether Lactobacillus colonization promotes normalization and maintenance of pH and Nugent score. The study was a multicenter, randomized, double-blind, and placebo-controlled trial. Altogether, 376 women were assessed for eligibility, and signed informed consent. One hundred and sixty eligible women with abnormal, also called intermediate, vaginal microflora, as indicated by a Nugent score of 4-6 and pH >4.5 and zero or low Lactobacillus count, were randomized. Each participant was examined four times during the study. Women were randomly allocated to receive either the probiotic preparation inVag(®), or a placebo (one capsule for seven consecutive days vaginally). The product inVag includes the probiotic strains Lactobacillus fermentum 57A, Lactobacillus plantarum 57B, and Lactobacillus gasseri 57C. We took vaginal swabs during visits I, III, and IV to determine the presence and abundance of bacteria from the Lactobacillus genus, measure the pH, and estimate the Nugent score. Drug safety evaluation was based on analysis of the types and occurrence of adverse events. Administration of inVag contributed to a significant decrease (between visits) in both vaginal pH (P<0.05) and Nugent score (P<0.05), and a significant increase in the abundance of Lactobacillus between visit I and visits III and IV (P<0.05). Molecular typing revealed the presence of Lactobacillus strains originating from inVag in 82% of women taking the drug at visit III, and 47.5% at visit IV. There was no serious adverse event related to inVag administration during the study. The probiotic inVag is safe for administration to sustainably restore the healthy vaginal microbiota, as demonstrated by predominance of the Lactobacillus bacteria in vaginal microbiota.

Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial

PubMed Central

Tomusiak, Anna; Strus, Magdalena; Heczko, Piotr B; Adamski, Paweł; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena

2015-01-01

Objective The main objective of this study was to evaluate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether Lactobacillus colonization promotes normalization and maintenance of pH and Nugent score. Patients and methods The study was a multicenter, randomized, double-blind, and placebo-controlled trial. Altogether, 376 women were assessed for eligibility, and signed informed consent. One hundred and sixty eligible women with abnormal, also called intermediate, vaginal microflora, as indicated by a Nugent score of 4–6 and pH >4.5 and zero or low Lactobacillus count, were randomized. Each participant was examined four times during the study. Women were randomly allocated to receive either the probiotic preparation inVag®, or a placebo (one capsule for seven consecutive days vaginally). The product inVag includes the probiotic strains Lactobacillus fermentum 57A, Lactobacillus plantarum 57B, and Lactobacillus gasseri 57C. We took vaginal swabs during visits I, III, and IV to determine the presence and abundance of bacteria from the Lactobacillus genus, measure the pH, and estimate the Nugent score. Drug safety evaluation was based on analysis of the types and occurrence of adverse events. Results Administration of inVag contributed to a significant decrease (between visits) in both vaginal pH (P<0.05) and Nugent score (P<0.05), and a significant increase in the abundance of Lactobacillus between visit I and visits III and IV (P<0.05). Molecular typing revealed the presence of Lactobacillus strains originating from inVag in 82% of women taking the drug at visit III, and 47.5% at visit IV. There was no serious adverse event related to inVag administration during the study. Conclusion The probiotic inVag is safe for administration to sustainably restore the healthy vaginal microbiota, as demonstrated by predominance of the Lactobacillus bacteria in vaginal microbiota. PMID:26451088

SPIRIT: A seamless phase I/II randomized design for immunotherapy trials.

PubMed

Guo, Beibei; Li, Daniel; Yuan, Ying

2018-06-07

Immunotherapy-treatments that enlist the immune system to battle tumors-has received widespread attention in cancer research. Due to its unique features and mechanisms for treating cancer, immunotherapy requires novel clinical trial designs. We propose a Bayesian seamless phase I/II randomized design for immunotherapy trials (SPIRIT) to find the optimal biological dose (OBD) defined in terms of the restricted mean survival time. We jointly model progression-free survival and the immune response. Progression-free survival is used as the primary endpoint to determine the OBD, and the immune response is used as an ancillary endpoint to quickly screen out futile doses. Toxicity is monitored throughout the trial. The design consists of two seamlessly connected stages. The first stage identifies a set of safe doses. The second stage adaptively randomizes patients to the safe doses identified and uses their progression-free survival and immune response to find the OBD. The simulation study shows that the SPIRIT has desirable operating characteristics and outperforms the conventional design. Copyright © 2018 John Wiley & Sons, Ltd.

Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

PubMed Central

Kaufman, Peter A.; Awada, Ahmad; Twelves, Chris; Yelle, Louise; Perez, Edith A.; Velikova, Galina; Olivo, Martin S.; He, Yi; Dutcus, Corina E.; Cortes, Javier

2015-01-01

Purpose This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Patients and Methods Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Results Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. Conclusion In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS. PMID:25605862

Waveform Design for Multimedia Airborne Networks: Robust Multimedia Data Transmission in Cognitive Radio Networks

DTIC Science & Technology

2011-03-01

at the sensor. According to Candes, Tao and Romberg [1], a small number of random projections of a signal that is compressible is all the...Projection of Signal Transform i. DWT ii. FFT iii. DCT Solve the Minimization problem Reconstruct Signal Channel (AWGN ) De -noise Signal Original...Signal (Noisy) Random Projection of Signal Transform i. DWT ii. FFT iii. DCT Solve the Minimization problem Reconstruct Signal Channel (Noiseless) De

Non-invasive high-intensity focused ultrasound for UV-induced hyperpigmentation in Fitzpatrick skin types III and IV: a prospective, randomized, controlled, evaluator-blinded trial.

PubMed

Vachiramon, Vasanop; Jurairattanaporn, Natthachat; Harnchoowong, Sarawin; Chayavichitsilp, Pamela

2018-02-01

Skin hyperpigmentation is a frequently encountered problem, particularly in darker skin types. Unfortunately, standard treatments for this condition have shown disappointing results. High-intensity focused ultrasound (HIFU) is commonly indicated for skin laxity, but recently was used to treat UV-induced hyperpigmentation in animal models. This study is aimed to evaluate the efficacy and safety of high-intensity focused ultrasound for UVB-induced hyperpigmentation in human subjects. A randomized, evaluator-blinded pilot study was conducted on 20 subjects. Each subject was induced three hyperpigmentary spots by local broadband UVB. After 2 weeks, each spot was randomly allocated to control, low-energy, and high-energy HIFU. Subjects were instructed to follow up weekly for a duration of 1 month. Lightness index measurements, mean improvement scores, subjects' satisfaction, pain scores, and side effects were evaluated. All 20 subjects completed the study. Fourteen subjects had Fitzpatrick (FPT) skin type III and six subjects had FPT skin type IV. Twelve subjects showed greater improvement at control sites while eight subjects showed greater improvement at HIFU-treated sites. In FPT skin type III, HIFU appeared to be inferior to control in both lightness index and mean improvement scores, but in FPT skin type IV, HIFU had greater lightness index improvement and higher improvement scores than control. Side effects were more frequent in high-energy-treated areas. Focused ultrasound may be offered in some patients with hyperpigmentary conditions. More research is needed to determine proper energy settings for optimal outcome.

Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins

PubMed Central

Furtado, Jeremy D.; Wedel, Mark K.; Sacks, Frank M.

2012-01-01

Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III–containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38–42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III–containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors. PMID:22301884

Development of Ultra-Low Noise, High Performance III-V Quantum Well Infrared Photodetectors (QWIPs) for Focal Plane Array Staring Image Sensor Systems

DTIC Science & Technology

1993-11-01

Development of Ultra-Low Noise , High Performance III-V Quantum Well Infrared Photodetectors ( QWIPs )I for Focal Plane Array Staring Image Sensor Systems...experimental studies of dark current, photocurrent, noise fig- ures optical absorption, spectral responsivity and detectivity for different types of QWIPs ...the Boltzmann constant, and T is the temperature. S The noise in the QWIPs is mainly due to the random fluctuations of thermally excited carriers. The

[Prospective randomized study regarding the effect of the preoperative antibiotic and chlorhexidine rinse on wound healing after mandibular third molar surgery].

PubMed

Kaposvári, István; Körmöczi, Kinga; László, Zsuzsa Beáta; Oberna, Ferenc; Horváth, Ferenc; Joób-Fancsaly, Árpád

2017-01-01

The study compares the antibiotic prophylaxis combined with postoperative antibiotic therapy to preoperative chlorhexidine rinse combined with postoperative antibiotic therapy in preventing complications after surgical removal of a mandibular third molar. 71 healthy patients in four groups were enrolled in the study: I. prophylactic dose of 2000 mg of amoxicillin clavulanate, continued with amoxicillin clavulanate postoperatively; II. prophylactic dose of 600 mg of clindamycin, continued with clindamycin postoperatively; III. prophylactic chlorhexidin rinsing, continued randomized amoxicillin clavulanate or clindamycin postoperatively; IV. control, with clindamycin postoperatively. The pain was smaller in the prophylaxis groups. Alveolitis occurred only in the control group: 2 patients. Wound opening occurred in 22,2 % in group IV., 14,2 % in group II, 10 % in group I., 5 % in group III. We consider completing the indicated postoperative antibiotic prescription with antibiotic or antiseptic prophylaxis. Chlorhexidin prophylaxis could have the same positive effect. Orv. Hetil., 2017, 158(1), 13-19.

Constraints on Nonlinear and Stochastic Growth Theories for Type 3 Solar Radio Bursts from the Corona to 1 AU

NASA Technical Reports Server (NTRS)

Cairns, Iver H.; Robinson, P. A.

1998-01-01

Existing, competing theories for coronal and interplanetary type III solar radio bursts appeal to one or more of modulational instability, electrostatic (ES) decay processes, or stochastic growth physics to preserve the electron beam, limit the levels of Langmuir-like waves driven by the beam, and produce wave spectra capable of coupling nonlinearly to generate the observed radio emission. Theoretical constraints exist on the wavenumbers and relative sizes of the wave bandwidth and nonlinear growth rate for which Langmuir waves are subject to modulational instability and the parametric and random phase versions of ES decay. A constraint also exists on whether stochastic growth theory (SGT) is appropriate. These constraints are evaluated here using the beam, plasma, and wave properties (1) observed in specific interplanetary type III sources, (2) predicted nominally for the corona, and (3) predicted at heliocentric distances greater than a few solar radii by power-law models based on interplanetary observations. It is found that the Langmuir waves driven directly by the beam have wavenumbers that are almost always too large for modulational instability but are appropriate to ES decay. Even for waves scattered to lower wavenumbers (by ES decay, for instance), the wave bandwidths are predicted to be too large and the nonlinear growth rates too small for modulational instability to occur for the specific interplanetary events studied or the great majority of Langmuir wave packets in type III sources at arbitrary heliocentric distances. Possible exceptions are for very rare, unusually intense, narrowband wave packets, predominantly close to the Sun, and for the front portion of very fast beams traveling through unusually dilute, cold solar wind plasmas. Similar arguments demonstrate that the ES decay should proceed almost always as a random phase process rather than a parametric process, with similar exceptions. These results imply that it is extremely rare for modulational instability or parametric decay to proceed in type III sources at any heliocentric distance: theories for type III bursts based on modulational instability or parametric decay are therefore not viable in general. In contrast, the constraint on SGT can be satisfied and random phase ES decay can proceed at all heliocentric distances under almost all circumstances. (The contrary circumstances involve unusually slow, broad beams moving through unusually hot regions of the Corona.) The analyses presented here strongly justify extending the existing SGT-based model for interplanetary type III bursts (which includes SGT physics, random phase ES decay, and specific electromagnetic emission mechanisms) into a general theory for type III bursts from the corona to beyond 1 AU. This extended theory enjoys strong theoretical support, explains the characteristics of specific interplanetary type III bursts very well, and can account for the detailed dynamic spectra of type III bursts from the lower corona and solar wind.

Milrinone, a phosphodiesterase III inhibitor, prevents reduction of jugular bulb saturation during rewarming from hypothermic cardiopulmonary bypass.

PubMed

Iritakenishi, T; Hayashi, Y; Yamanaka, H; Kamibayashi, T; Ueda, K; Mashimo, T

2012-01-01

Inadequate cerebral oxygen balance during cardiopulmonary bypass may cause neuropsychological dysfunction. Milrinone, a phosphodiesterase III inhibitor, augments cerebral blood flow by direct vasodilatation. We conducted a prospective, randomized study in patients undergoing cardiac surgery with cardiopulmonary bypass to clarify the clinical efficacy of milrinone in the imbalance of cerebral oxygen supply and demand during the rewarming period of cardiopulmonary bypass. This is a prospective, randomized and placebo-controlled study. After anesthesia, a 5.5 F fiberoptic oximeter catheter was inserted into the right jugular bulb retrogradely for monitoring the jugular venous oxyhemoglobin saturation (SjO(2)). Patients were randomly assigned to two groups, one receiving a continuous infusion of milrinone, 0.5 µg/kg/min during hypothermic cardiopulmonary bypass, and the other receiving saline as control. Milrinone significantly prevented the reduction of the jugular venous oxyhemoglobin saturation at 10 minutes from the start of rewarming compared with the control group, but did not do so from 10 to 20 minutes after rewarming. Milrinone suppresses the reduction of SjO(2) and improves the balance of cerebral oxygen supply and demand during the early rewarming period of hypothermic cardiopulmonary bypass.

Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

PubMed

Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

2016-02-01

Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

Endovascular Therapy Is Effective and Safe for Patients With Severe Ischemic Stroke: Pooled Analysis of Interventional Management of Stroke III and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands Data.

PubMed

Broderick, Joseph P; Berkhemer, Olvert A; Palesch, Yuko Y; Dippel, Diederik W J; Foster, Lydia D; Roos, Yvo B W E M; van der Lugt, Aad; Tomsick, Thomas A; Majoie, Charles B L M; van Zwam, Wim H; Demchuk, Andrew M; van Oostenbrugge, Robert J; Khatri, Pooja; Lingsma, Hester F; Hill, Michael D; Roozenbeek, Bob; Jauch, Edward C; Jovin, Tudor G; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A; Goyal, Mayank; Schonewille, Wouter J; Mazighi, Mikael; Engelter, Stefan T; Anderson, Craig S; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J; Janis, L Scott; Simpson, Kit N

2015-12-01

We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (National Institutes of Health Stroke Scale score, ≥20) after a prespecified analysis plan. The pooled analysis of the Interventional Management of Stroke III (IMS III) and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trials included participants with an National Institutes of Health Stroke Scale score of ≥20 before intravenous tissue-type plasminogen activator (tPA) treatment (IMS III) or randomization (MR CLEAN) who were treated with intravenous tPA ≤3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy after intravenous tPA would have improved 90-day outcome (distribution of modified Rankin Scale scores), when compared with those who received intravenous tPA alone. Among 342 participants in the pooled analysis (194 from IMS III and 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared with the intravenous tPA group (adjusted odds ratio, 1.78; 95% confidence interval, 1.20-2.66). In the logistic regression model of the dichotomous outcome (modified Rankin Scale score, 0-2, or functional independence), the endovascular group had superior outcomes (adjusted odds ratio, 1.97; 95% confidence interval, 1.09-3.56). Functional independence (modified Rankin Scale score, ≤2) at 90 days was 25% in the endovascular group when compared with 14% in the intravenous tPA group. Endovascular therapy after intravenous tPA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424 (IMS III) and ISRCTN10888758 (MR CLEAN). © 2015 American Heart Association, Inc.

A Stepwise Integrated Approach to Personalized Risk Predictions in Stage III Colorectal Cancer.

PubMed

Salvucci, Manuela; Würstle, Maximilian L; Morgan, Clare; Curry, Sarah; Cremona, Mattia; Lindner, Andreas U; Bacon, Orna; Resler, Alexa J; Murphy, Áine C; O'Byrne, Robert; Flanagan, Lorna; Dasgupta, Sonali; Rice, Nadege; Pilati, Camilla; Zink, Elisabeth; Schöller, Lisa M; Toomey, Sinead; Lawler, Mark; Johnston, Patrick G; Wilson, Richard; Camilleri-Broët, Sophie; Salto-Tellez, Manuel; McNamara, Deborah A; Kay, Elaine W; Laurent-Puig, Pierre; Van Schaeybroeck, Sandra; Hennessy, Bryan T; Longley, Daniel B; Rehm, Markus; Prehn, Jochen H M

2017-03-01

Purpose: Apoptosis is essential for chemotherapy responses. In this discovery and validation study, we evaluated the suitability of a mathematical model of apoptosis execution (APOPTO-CELL) as a stand-alone signature and as a constituent of further refined prognostic stratification tools. Experimental Design: Apoptosis competency of primary tumor samples from patients with stage III colorectal cancer ( n = 120) was calculated by APOPTO-CELL from measured protein concentrations of Procaspase-3, Procaspase-9, SMAC, and XIAP. An enriched APOPTO-CELL signature (APOPTO-CELL-PC3) was synthesized to capture apoptosome-independent effects of Caspase-3. Furthermore, a machine learning Random Forest approach was applied to APOPTO-CELL-PC3 and available molecular and clinicopathologic data to identify a further enhanced signature. Association of the signature with prognosis was evaluated in an independent colon adenocarcinoma cohort (TCGA COAD, n = 136). Results: We identified 3 prognostic biomarkers ( P = 0.04, P = 0.006, and P = 0.0004 for APOPTO-CELL, APOPTO-CELL-PC3, and Random Forest signatures, respectively) with increasing stratification accuracy for patients with stage III colorectal cancer.The APOPTO-CELL-PC3 signature ranked highest among all features. The prognostic value of the signatures was independently validated in stage III TCGA COAD patients ( P = 0.01, P = 0.04, and P = 0.02 for APOPTO-CELL, APOPTO-CELL-PC3, and Random Forest signatures, respectively). The signatures provided further stratification for patients with CMS1-3 molecular subtype. Conclusions: The integration of a systems-biology-based biomarker for apoptosis competency with machine learning approaches is an appealing and innovative strategy toward refined patient stratification. The prognostic value of apoptosis competency is independent of other available clinicopathologic and molecular factors, with tangible potential of being introduced in the clinical management of patients with stage III colorectal cancer. Clin Cancer Res; 23(5); 1200-12. ©2016 AACR . ©2016 American Association for Cancer Research.

Armodafinil in Reducing Cancer-Related Fatigue in Patients With High Grade Glioma | Division of Cancer Prevention

Cancer.gov

This randomized phase III trial studies armodafinil to see how well it works in reducing cancer-related fatigue in patients with high grade glioma. Armodafinil may help relieve fatigue in patients with high grade glioma. |

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial.

PubMed

Liang, J; Bi, N; Wu, S; Chen, M; Lv, C; Zhao, L; Shi, A; Jiang, W; Xu, Y; Zhou, Z; Wang, W; Chen, D; Hui, Z; Lv, J; Zhang, H; Feng, Q; Xiao, Z; Wang, X; Liu, L; Zhang, T; Du, L; Chen, W; Shyr, Y; Yin, W; Li, J; He, J; Wang, L

2017-04-01

The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%-28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55-1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. NCT01494558. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bayesian randomized clinical trials: From fixed to adaptive design.

PubMed

Yin, Guosheng; Lam, Chi Kin; Shi, Haolun

2017-08-01

Randomized controlled studies are the gold standard for phase III clinical trials. Using α-spending functions to control the overall type I error rate, group sequential methods are well established and have been dominating phase III studies. Bayesian randomized design, on the other hand, can be viewed as a complement instead of competitive approach to the frequentist methods. For the fixed Bayesian design, the hypothesis testing can be cast in the posterior probability or Bayes factor framework, which has a direct link to the frequentist type I error rate. Bayesian group sequential design relies upon Bayesian decision-theoretic approaches based on backward induction, which is often computationally intensive. Compared with the frequentist approaches, Bayesian methods have several advantages. The posterior predictive probability serves as a useful and convenient tool for trial monitoring, and can be updated at any time as the data accrue during the trial. The Bayesian decision-theoretic framework possesses a direct link to the decision making in the practical setting, and can be modeled more realistically to reflect the actual cost-benefit analysis during the drug development process. Other merits include the possibility of hierarchical modeling and the use of informative priors, which would lead to a more comprehensive utilization of information from both historical and longitudinal data. From fixed to adaptive design, we focus on Bayesian randomized controlled clinical trials and make extensive comparisons with frequentist counterparts through numerical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Antitumor Effects of Somatostatin Analogs in Neuroendocrine Tumors

PubMed Central

Dubé, Pierre; Rinke, Anja

2012-01-01

Background. For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it has been suggested that somatostatin analogs may provide direct and indirect antitumor effects in secretory and nonsecretory NETs in addition to symptom control in secretory NETs. Methods. A systematic review of MEDLINE was conducted to identify studies that investigated the antitumor effects of octreotide or lanreotide for patients with NETs. Additional studies not published in the peer-reviewed literature were identified by searching online abstracts. Results. In all, 17 octreotide trials and 11 lanreotide trials that included antitumor effects were identified. Partial response rates were between 0% and 31%, and stable disease rates were between 15% and 89%. Octreotide was the only somatostatin analog for which results of a phase III, randomized, placebo-controlled clinical trial that investigated antitumor effects were published. After 6 months of treatment in this randomized phase III trial, stable disease was observed in 67% of patients (hazard ratio for time to disease progression: 0.34; 95% confidence interval: 0.20–0.59; p = .000072). Conclusions. In addition to symptom control for NETs, the data support an antitumor effect of somatostatin analogs and suggest that they may slow tumor growth. Long-acting repeatable octreotide has been shown to have an antitumor effect in a randomized phase III trial in midgut NETs, whereas results are pending in a corresponding controlled trial with lanreotide for patients with intestinal and pancreatic primary NETs. PMID:22628056

A prospective, randomized trial comparing the short- and long-term results of doppler-guided transanal hemorrhoid dearterialization with mucopexy versus excision hemorrhoidectomy for grade III hemorrhoids.

PubMed

De Nardi, Paola; Capretti, Giovanni; Corsaro, Antonino; Staudacher, Carlo

2014-03-01

Few randomized trials have compared the results of Doppler-guided transanal hemorrhoid dearterialization with mucopexy and excisional open hemorrhoidectomy. Few studies have reported long-term results. The aim of this study is to evaluate the results of Doppler-guided transanal hemorrhoid dearterialization with mucopexy compared with excisional open hemorrhoidectomy in patients with grade III hemorrhoids. This is a prospective randomized study registered at clinicaltrials.gov (NCT01263431). A power analysis assessed the study's sample size. Patients were randomly assigned to undergo either hemorrhoidectomy or Doppler-guided hemorrhoid dearterialization plus mucopexy. The χ test, Mann-Whitney U test, Student t test, and a regression model were used, as appropriate. This study was conducted at the Department of Surgery, San Raffaele Scientific Institute, Milan, Italy. Fifty consecutive patients were treated for grade III hemorrhoids from July to November 2010. The primary outcome was postoperative pain. The secondary outcomes included postoperative morbidity, the resumption of social and/or working activity, patient satisfaction, and the relapse of symptoms at 1 and 24 months. No major complications occurred in either group. The median visual analog scale scores for pain in the hemorrhoidectomy and Doppler-guided dearterialization plus mucopexy groups on days 1, 7, 14, and 30 were 7 vs 5.5, 3 vs 2.5, 1 vs 0, and 0 vs 0 (p> 0.05). The median work resumption day was the 22nd in the hemorrhoidectomy group and the 10th in the Doppler-guided dearterialization plus mucopexy group (p = 0.09). Patient satisfaction at 1 and 24 postoperative months, with the use of a 4-point scale, was 3 vs 4 and 4 vs 4 (p > 0.05). During the follow-up, 2 patients in the dearterialization group required ambulatory treatment, and 1 patient in each group required further surgery for symptom relapse. Nonvalidated questionnaires were used in the follow-up. Cost analysis was not performed. Compared with hemorrhoidectomy, dearterialization with mucopexy resulted in similar postoperative pain and morbidity, and a similar long-term cure rate.

Switching From Reference Adalimumab to SB5 (Adalimumab Biosimilar) in Patients With Rheumatoid Arthritis: Fifty-Two-Week Phase III Randomized Study Results.

PubMed

Weinblatt, Michael E; Baranauskaite, Asta; Dokoupilova, Eva; Zielinska, Agnieszka; Jaworski, Janusz; Racewicz, Artur; Pileckyte, Margarita; Jedrychowicz-Rosiak, Krystyna; Baek, Inyoung; Ghil, Jeehoon

2018-06-01

The 24-week equivalent efficacy and comparable safety results of the biosimilar SB5 and reference adalimumab (ADA) from the phase III randomized study in patients with moderate-to-severe rheumatoid arthritis (RA) have been reported previously. We undertook this transition study to evaluate patients who switched from ADA to SB5 or who continued to receive SB5 or ADA up to 52 weeks. In this phase III study, patients were initially randomized 1:1 to receive SB5 or ADA (40 mg subcutaneously every other week). At 24 weeks, patients receiving ADA were rerandomized 1:1 to continue with ADA (ADA/ADA group) or to switch to SB5 (ADA/SB5 group) up to week 52; patients receiving SB5 continued with SB5 for 52 weeks (SB5 group). Efficacy, safety, and immunogenicity were evaluated up to 52 weeks. The full analysis set population consisted of 542 patients (269 in the SB5 group, 273 in the ADA overall group [patients who were randomized to receive ADA at week 0], 125 in the ADA/SB5 group, and 129 in the ADA/ADA group). The percentages of patients meeting the American College of Rheumatology 20%, 50%, or 70% improvement criteria (achieving an ACR20, ACR50, or ACR70 response) at week 24 were maintained after the transition from ADA to SB5, and these response rates were comparable across treatment groups throughout the study. ACR20 response rates ranged from 73.4% to 78.8% at week 52. Radiographic progression was minimal and comparable across treatment groups. The safety profile and the incidence of antidrug antibodies were comparable across treatment groups after transition. SB5 was well tolerated over 1 year in patients with RA, with efficacy, safety, and immunogenicity comparable to those of ADA. Switching from ADA to SB5 had no treatment-emergent issues such as increased adverse events, increased immunogenicity, or loss of efficacy. © 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Prophylactic Cranial Irradiation Versus Observation in Radically Treated Stage III Non-Small-Cell Lung Cancer: A Randomized Phase III NVALT-11/DLCRG-02 Study.

PubMed

De Ruysscher, Dirk; Dingemans, Anne-Marie C; Praag, John; Belderbos, Jose; Tissing-Tan, Caroline; Herder, Judith; Haitjema, Tjeerd; Ubbels, Fred; Lagerwaard, Frank; El Sharouni, Sherif Y; Stigt, Jos A; Smit, Egbert; van Tinteren, Harm; van der Noort, Vincent; Groen, Harry J M

2018-05-22

Purpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non-small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC-staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging-were randomly assigned to either observation or PCI after concurrent/sequential chemoradiotherapy with or without surgery. The primary end point-development of symptomatic brain metastases at 24 months-was defined as one or a combination of key symptoms that suggest brain metastases-signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurologic symptoms-and magnetic resonance imaging or computed tomography demonstrating the existence of brain metastasis. Adverse effects, survival, quality of life, quality-adjusted survival, and health care costs were secondary end points. Results Between 2009 and 2015, 175 patients were randomly assigned: 87 received PCI and 88 underwent observation only. Median follow-up was 48.5 months (95% CI, 39 to 54 months). Six (7.0%) of 86 patients in the PCI group and 24 (27.2%) of 88 patients in the control group had symptomatic brain metastases ( P = .001). PCI significantly increased the time to develop symptomatic brain metastases (hazard ratio, 0.23; [95% CI, 0.09 to 0.56]; P = .0012). Median time to develop brain metastases was not reached in either arm. Overall survival was not significantly different between both arms. Grade 1 and 2 memory impairment (26 of 86 v seven of 88 patients) and cognitive disturbance (16 of 86 v three of 88 patients) were significantly increased in the PCI arm. Quality of life was only decreased 3 months post-PCI and was similar to the observation arm thereafter. Conclusion PCI significantly decreased the proportion of patients who developed symptomatic brain metastases with an increase of low-grade toxicity.

Efficacy of tramadol and butorphanol pretreatment in reducing pain on propofol injection: A placebo-controlled randomized study.

PubMed

Singh, Arvinderpal; Sharma, Geeta; Gupta, Ruchi; Kumari, Anita; Tikko, Deepika

2016-01-01

Pain of propofol injection has been recalled by many patients as the most painful part of the induction of anesthesia. Tramadol and butorphanol are commonly used analgesics for perioperative analgesia in anesthesia practice. However, their potential to relieve propofol injection pain still needs to be explored. A randomized, double-blind, placebo-controlled study was conducted on 90 American Society of Anesthesiologists I and II adult patients undergoing elective surgery under general anesthesia with propofol as an induction agent. Consecutive sampling technique with random assignment was used to allocate three groups of 30 patients each. Group I patients received an injection of normal saline 3 ml intravenously (placebo) while Group II and Group III patients received injection of tramadol 50 mg and butorphanol 1 mg intravenously, respectively. Before induction of anesthesia patients were asked about the intensity of pain on propofol injection by using visual analog scale (VAS) before the loss of consciousness. Descriptive statistics and analysis of variance with Chi-square test were used to analyze the data. The value of P < 0.05 was considered as a significant and P < 0.0001 as highly significant. The incidence of pain in Group I was observed in 80% of the patients, while it was observed in 23.33% and 20% of patients in Group II and III, respectively. Mean VAS scores were 2.27 ± 1.51, 1.14 ± 1.74, and 1.03 ± 1.72 in Group I, II, and Group III patients, respectively. The incidence of pruritus was 10% and 6.7% and erythema in 13.2% and 6.7% in Group II and III, respectively. Pretreatment with both butorphanol and tramadol significantly reduced pain on propofol injection; however, they exhibited comparable efficacy among each other. Thus, either of these two drugs can be considered for pretreatment to reduce propofol injection pain.

A Two Year Randomized Controlled Trial of Progressive Resistance Exercise for Parkinson’s Disease

PubMed Central

Corcos, Daniel M.; Robichaud, Julie A.; David, Fabian J.; Leurgans, Sue E.; Vaillancourt, David E.; Poon, Cynthia; Rafferty, Miriam R.; Kohrt, Wendy M.; Comella, Cynthia L.

2013-01-01

Background The effects of progressive resistance exercise (PRE) on the motor signs of Parkinson’s disease have not been studied in controlled trials. Our aim was to compare 6, 12, 18, and 24 month outcomes of patients with Parkinson’s disease who received PRE to a stretching, balance, and strengthening exercise program. Methods We conducted a randomized controlled trial between September 2007 and July 2011. Pairs of patients, matched by sex and off-medication Unified Parkinson’s Disease Rating Scale, motor subscale (UPDRS-III), were randomly assigned to the interventions with a 1:1 allocation ratio. The PRE group performed a weight lifting program. The Modified Fitness Counts (mFC) group performed a stretching, balance, and strengthening exercise program. Patients exercised two days per week for 24 months at a gym. A personal trainer directed both weekly sessions for the first six months and one weekly session after six months. The primary outcome was the off-medication UPDRS-III score. Patients were followed for 24 months at six-month intervals. Results Of 51 patients, 20 in PRE and 18 in mFC completed the trial. At 24 months, the mean off-medication UPDRS-III score decreased more with PRE than with mFC (mean difference: - 7·3 points; 95% CI: -11·3 to -3·6; P < 0·001). The PRE group had ten adverse events. The mFC group had seven adverse events. Conclusions PRE demonstrated a statistically and clinically significant reduction in UPDRS-III scores compared to mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs. PMID:23536417

RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia.

PubMed

Wolf, Sebastian; Balciuniene, Vilma Jurate; Laganovska, Guna; Menchini, Ugo; Ohno-Matsui, Kyoko; Sharma, Tarun; Wong, Tien Y; Silva, Rufino; Pilz, Stefan; Gekkieva, Margarita

2014-03-01

To compare the efficacy and safety of ranibizumab 0.5 mg, guided by visual acuity (VA) stabilization or disease activity criteria, versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV). Phase III, 12-month, randomized, double-masked, multicenter, active-controlled study. Patients (N = 277) with visual impairment due to myopic CNV. Patients were randomized to receive ranibizumab on day 1, month 1, and thereafter as needed guided by VA stabilization criteria (group I, n = 106); ranibizumab on day 1 and thereafter as needed guided by disease activity criteria (group II, n=116); or vPDT on day 1 and disease activity treated with ranibizumab or vPDT at investigators' discretion from month 3 (group III, n = 55). Mean average best-corrected visual acuity (BCVA) change from baseline to month 1 through months 3 (primary) and 6, mean BCVA change and safety over 12 months. Ranibizumab treatment in groups I and II was superior to vPDT based on mean average BCVA change from baseline to month 1 through month 3 (group I: +10.5, group II: +10.6 vs. group III: +2.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; both P<0.0001). Ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month 1 through month 6 (group II: +11.7 vs. group I: +11.9 ETDRS letters; P<0.00001). Mean BCVA change from baseline to month 12 was +13.8 (group I), +14.4 (group II), and +9.3 ETDRS letters (group III). At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab injections over 12 months. No deaths or cases of endophthalmitis and myocardial infarction occurred. Ranibizumab treatment, irrespective of retreatment criteria, provided superior BCVA gains versus vPDT up to month 3. Ranibizumab treatment guided by disease activity criteria was noninferior to VA stabilization criteria up to month 6. Over 12 months, individualized ranibizumab treatment was effective in improving and sustaining BCVA and was generally well tolerated in patients with myopic CNV. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A Phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6 for lower rectal cancer with suspected lateral pelvic node metastasis: Japan Clinical Oncology Group Study JCOG1310 (PRECIOUS study).

PubMed

Ohue, Masayuki; Iwasa, Satoru; Kanemitsu, Yukihide; Hamaguchi, Tetsuya; Shiozawa, Manabu; Ito, Masaaki; Yasui, Masayoshi; Katayama, Hiroshi; Mizusawa, Junki; Shimada, Yasuhiro

2017-01-01

A randomized phase II/III trial was started in May 2015 comparing perioperative versus postoperative chemotherapy with modified infusional fluorouracil and folinic acid with oxaliplatin for lower rectal cancer patients with suspected lateral pelvic node metastasis. The standard arm is total mesorectal excision or tumor-specific mesorectal excision with lateral pelvic node dissection (LND) followed by postoperative chemotherapy (modified infusional fluorouracil and folinic acid with oxaliplatin; 12 cycles). The experimental (perioperative chemotherapy) arm is six courses of modified infusional fluorouracil and folinic acid with oxaliplatin before and six courses after total mesorectal excision with lateral pelvic node dissection. The aim of this trial is to confirm the superiority of perioperative chemotherapy. A total of 330 patients will be enrolled over 7 years. The primary endpoint in Phase II part is proportion of R0 resection and that in Phase III part is overall survival. Secondary endpoints are progression-free survival, local progression-free survival, etc. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000017603 [http://www.umin.ac.jp/ctr/index-j.htm]. © The Author 2016. Published by Oxford University Press.

Validity of Random Short Forms: III. Wechsler's Intelligence Scales.

ERIC Educational Resources Information Center

Silverstein, A. B.

1983-01-01

Formulas for estimating the validity of random short forms were applied to the standardization data for the Wechsler Adult Intelligence Scale-Revised, the Minnesota Multiphasic Personality Inventory, and the Marlowe-Crowne Social Desirability Scale. These formulas demonstrated how much "better than random" the best short forms of these…

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), andmore » the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. Conclusions: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.« less

A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).

PubMed

Martín, M; Chan, A; Dirix, L; O'Shaughnessy, J; Hegg, R; Manikhas, A; Shtivelband, M; Krivorotko, P; Batista López, N; Campone, M; Ruiz Borrego, M; Khan, Q J; Beck, J T; Ramos Vázquez, M; Urban, P; Goteti, S; Di Tomaso, E; Massacesi, C; Delaloge, S

2017-02-01

Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models. BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease. Patients were stratified by PI3K pathway activation and hormone receptor status. The primary endpoint was progression-free survival (PFS) in the full and PI3K pathway-activated populations. An adaptive interim analysis was planned following the phase II part of the study, after ≥125 PFS events had occurred in the full population, to decide whether the study would enter phase III (in the full or PI3K pathway-activated population) or be stopped for futility. As of August 2014, 416 patients were randomized to receive buparlisib (207) or placebo (209) with paclitaxel. At adaptive interim analysis, there was no improvement in PFS with buparlisib versus placebo in the full (median PFS 8.0 versus 9.2 months, hazard ratio [HR] 1.18), or PI3K pathway-activated population (median PFS 9.1 versus 9.2 months, HR 1.17). The study met protocol-specified criteria for futility in both populations, and phase III was not initiated. Median duration of study treatment exposure was 3.5 months in the buparlisib arm versus 4.6 months in the placebo arm. The most frequent adverse events with buparlisib plus paclitaxel (≥40% of patients) were diarrhea, alopecia, rash, nausea, and hyperglycemia. Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population. Consequently, the trial was stopped for futility at the end of phase II. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Confirmation of model-based dose selection for a Japanese phase III study of rivaroxaban in non-valvular atrial fibrillation patients.

PubMed

Kaneko, Masato; Tanigawa, Takahiko; Hashizume, Kensei; Kajikawa, Mariko; Tajiri, Masahiro; Mueck, Wolfgang

2013-01-01

This study was designed to confirm the appropriateness of the dose setting for a Japanese phase III study of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), which had been based on model simulation employing phase II study data. The previously developed mixed-effects pharmacokinetic/pharmacodynamic (PK-PD) model, which consisted of an oral one-compartment model parameterized in terms of clearance, volume and a first-order absorption rate, was rebuilt and optimized using the data for 597 subjects from the Japanese phase III study, J-ROCKET AF. A mixed-effects modeling technique in NONMEM was used to quantify both unexplained inter-individual variability and inter-occasion variability, which are random effect parameters. The final PK and PK-PD models were evaluated to identify influential covariates. The empirical Bayes estimates of AUC and C(max) from the final PK model were consistent with the simulated results from the Japanese phase II study. There was no clear relationship between individual estimated exposures and safety-related events, and the estimated exposure levels were consistent with the global phase III data. Therefore, it was concluded that the dose selected for the phase III study with Japanese NVAF patients by means of model simulation employing phase II study data had been appropriate from the PK-PD perspective.

Efficacy and tolerability of two different formulations of atorvastatin in Korean patients with hypercholesterolemia: a multicenter, prospective, randomized clinical trial.

PubMed

Lee, Ju-Hee; Kim, Sang-Hyun; Choi, Dong-Ju; Tahk, Seung-Jea; Yoon, Jung-Han; Choi, Si Wan; Hong, Taek-Jong; Kim, Hyo-Soo

2017-01-01

This study was designed to compare the efficacy and tolerability of the generic formulation (Atorva ® ) and the reference formulation (Lipitor ® ) of atorvastatin, both at a dosage of 20 mg once daily. This study was a prospective open-label, randomized controlled study. Hypercholesterolemic patients who had not achieved low-density lipoprotein (LDL) cholesterol goals according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline were randomized to generic formulation or reference formulation of atorvastatin. The primary end point was the percent change of blood LDL cholesterol at 8 weeks from the baseline. The secondary end points included the percent changes of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1) levels, the percent changes of ApoB/ApoA1 and total cholesterol/HDL cholesterol ratios, and the change in high-sensitivity C-reactive protein (hsCRP) levels. The LDL cholesterol goal achievement rate according to the NCEP-ATP III guideline was also evaluated. Three hundred and seventy-six patients were randomized, and 346 patients (176 in the generic group and 170 in the reference group) completed the study. After the 8 weeks of treatment, LDL cholesterol level was significantly decreased in both the groups, and the decrement was comparable between the two groups (-43.9%±15.3% in the generic group, -43.3%±17.0% in the reference group, P =0.705). The percent changes of total cholesterol, HDL cholesterol, TG, ApoB, ApoA1, ApoB/ApoA1 ratio, total cholesterol/HDL cholesterol ratio, and hsCRP showed insignificant difference between the two groups. However, LDL cholesterol goal achievement rate was significantly higher in the generic group compared to the reference group (90.6% vs 83.0%, P =0.039) in per-protocol analysis. Adverse event rate was comparable between the two groups (12.0% vs 13.7%, P =0.804). The generic formulation of atorvastatin 20 mg was not inferior to the reference formulation of atorvastatin 20 mg in the management of hypercholesterolemia.

Efficacy and tolerability of two different formulations of atorvastatin in Korean patients with hypercholesterolemia: a multicenter, prospective, randomized clinical trial

PubMed Central

Lee, Ju-Hee; Kim, Sang-Hyun; Choi, Dong-Ju; Tahk, Seung-Jea; Yoon, Jung-Han; Choi, Si Wan; Hong, Taek-Jong; Kim, Hyo-Soo

2017-01-01

Purpose This study was designed to compare the efficacy and tolerability of the generic formulation (Atorva®) and the reference formulation (Lipitor®) of atorvastatin, both at a dosage of 20 mg once daily. Methods This study was a prospective open-label, randomized controlled study. Hypercholesterolemic patients who had not achieved low-density lipoprotein (LDL) cholesterol goals according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline were randomized to generic formulation or reference formulation of atorvastatin. The primary end point was the percent change of blood LDL cholesterol at 8 weeks from the baseline. The secondary end points included the percent changes of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1) levels, the percent changes of ApoB/ApoA1 and total cholesterol/HDL cholesterol ratios, and the change in high-sensitivity C-reactive protein (hsCRP) levels. The LDL cholesterol goal achievement rate according to the NCEP-ATP III guideline was also evaluated. Results Three hundred and seventy-six patients were randomized, and 346 patients (176 in the generic group and 170 in the reference group) completed the study. After the 8 weeks of treatment, LDL cholesterol level was significantly decreased in both the groups, and the decrement was comparable between the two groups (−43.9%±15.3% in the generic group, −43.3%±17.0% in the reference group, P=0.705). The percent changes of total cholesterol, HDL cholesterol, TG, ApoB, ApoA1, ApoB/ApoA1 ratio, total cholesterol/HDL cholesterol ratio, and hsCRP showed insignificant difference between the two groups. However, LDL cholesterol goal achievement rate was significantly higher in the generic group compared to the reference group (90.6% vs 83.0%, P=0.039) in per-protocol analysis. Adverse event rate was comparable between the two groups (12.0% vs 13.7%, P=0.804). Conclusion The generic formulation of atorvastatin 20 mg was not inferior to the reference formulation of atorvastatin 20 mg in the management of hypercholesterolemia. PMID:28814835

A prospective, randomized therapeutic trial for schistosomal specific nephropathy.

PubMed

Sobh, M A; Moustafa, F E; Sally, S M; Foda, M A; Deelder, A M; Ghoneim, M A

1989-11-01

In this work 26 patients with schistosomal specific nephropathy were randomly distributed among three groups. Group I cases were given anti-schistosomal drugs (oxamniquine and praziquantel), group II cases were given anti-schistosomal drugs plus prednisolone, and group III cases were given anti-schistosomal drugs plus cyclosporine. The schistosomal specificity of kidney lesions was assessed by detecting the schistosomal specific antigens (CAA and CCA) and antibodies deposited in the renal glomeruli of these patients. Patients who had another etiologic cause which may explain their kidney disease were not admitted to this study. After initiation of the treatment, patients were followed up every other week in the outpatient clinic for 12 months. Follow-up showed complete remission of proteinuria in two cases in group II (duration of remission was 4 and 8 months) and in one case in group III (duration of remission was 6 months) but in none in group I. Partial remission was observed in one case in group I, in three cases in group II and in one case in group III. During the observation period, improvement in kidney function was observed in two cases in group II but deterioration in kidney function was observed in one case in group I and in one other case in group III. We conclude that in patients with schistosomal nephropathy, none of the tried therapeutic regimens produce regression of the disease if given to patients with established disease.

Thermal conductivity of ternary III-V semiconductor alloys: The role of mass difference and long-range order

NASA Astrophysics Data System (ADS)

Mei, S.; Knezevic, I.

2018-03-01

Thermal transport in bulk ternary III-V arsenide (III-As) semiconductor alloys was investigated using equilibrium molecular dynamics with optimized Albe-Tersoff empirical interatomic potentials. Existing potentials for binary AlAs, GaAs, and InAs were optimized to match experimentally obtained acoustic-phonon dispersions and temperature-dependent thermal conductivity. Calculations of thermal transport in ternary III-Vs commonly employ the virtual-crystal approximation (VCA), where the structure is assumed to be a random alloy and all group-III atoms (cations) are treated as if they have an effective weighted-average mass. Here, we showed that it is critical to treat atomic masses explicitly and that the thermal conductivity obtained with explicit atomic masses differs considerably from the value obtained with the average VCA cation mass. The larger the difference between the cation masses, the poorer the VCA prediction for thermal conductivity. The random-alloy assumption in the VCA is also challenged because X-ray diffraction and transmission electron microscopy show order in InGaAs, InAlAs, and GaAlAs epilayers. We calculated thermal conductivity for three common types of order (CuPt-B, CuAu-I, and triple-period-A) and showed that the experimental results for In0.53Ga0.47As and In0.52Al0.48As, which are lattice matched to the InP substrate, can be reproduced in molecular dynamics simulation with 2% and 8% of random disorder, respectively. Based on our results, thermal transport in ternary III-As alloys appears to be governed by the competition between mass-difference scattering, which is much more pronounced than the VCA suggests, and the long-range order that these alloys support.

The Effect of Chin-cup Therapy in Class III Malocclusion: A Systematic Review

PubMed Central

Mousoulea, Sophia; Tsolakis, Ioannis; Ferdianakis, Efstratios; Tsolakis, Apostolos I.

2016-01-01

Background: The treatment of Class III malocclusion has been challenging for orthodontists. Among a plethora of treatment modalities, the chin-cup is considered a traditional appliance for early orthopedic intervention. Objective: The present study aims to investigate the current scientific evidence regarding the effectiveness of chin-cup therapy in Class III malocclusion of prognathic growing patients. Method: A systematic review of the literature was conducted using PubMed/Medline and the Cochrane Central Register of Controlled Trials from January 1954 to October 2015. Articles were selected based on established inclusion/ exclusion criteria. Results: The search strategy resulted in 3285 articles.14 studies were selected for the final analysis. They were all CCTs, 13 of retrospective and 1 of prospective design. Methodological quality was evaluated by a risk of bias assessment, as suggested by the Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies on Interventions. The reported evidence presented favorable short-term outcomes both in hard and soft tissues improving the Class III profile, as well as desirable dento-alveolar changes, positively affecting the Class III malocclusion. Conclusion: There is considerable agreement between studies that chin-cup therapy can be considered for the short-term treatment of growing patients with Class III malocclusion, as indicated by favorable changes both in the hard and soft tissues. The existence of considerable risk of bias in all selected studies and the unclear long-term effectiveness of chin-cup therapy highlight the need for further investigation to draw reliable conclusions. PMID:28077971

[Subset analysis of preoperative lymphocyte ratio in stage II or III colorectal cancer patients treated with oral tegafur-uracil and protein-bound polysaccharide K].

PubMed

Totsuka, Osamu; Kawate, Susumu; Hirai, Keitaro; Ogawa, Hiroomi; Toya, Hiroyuki; Yoshinari, Daisuke; Sunose, Yutaka; Takeyoshi, Izumi

2013-12-01

We have reported, in a randomized, controlled study, that tegafur-uracil(UFT)and protein-bound polysaccharide K(PSK)combination therapy significantly improves the 5-year disease-free survival rate and reduces the risk of recurrence compared to UFT alone for Stage II or III colorectal cancer. In this study, we examined the efficacy of PSK by stratifying patients according to the preoperative lymphocyte ratio(Lym). In a randomized, controlled study, 205 patients were eligible(137 in the UFT/PSK group and 68 in the UFT group). Of these, 193 patients with available preoperative Lym data were analysed(131 in the UFT/PSK group and 62 in the UFT group). Among patients with a preoperative Lym of <35%, the relapse-free survival(RFS)rate was 76.5% in the UFT/PSK group and 55.8% in the UFT group(p=0.008). However, in patients with a preoperative Lym of ≥35%, the RFS rate did not differ between the 2 groups. Similarly, overall survival was significantly higher in the UFT/PSK group than in the UFT group in patients with a preoperative Lym of <35%, whereas no intergroup difference was found among patients with a preoperative Lym of ≥35%. This study suggests that a low preoperative Lym is a good predictor for response to PSK in patients with Stage II or III colorectal cancer.

Effects of media violence on health-related outcomes among young men.

PubMed

Brady, Sonya S; Matthews, Karen A

2006-04-01

To test the effects of media violence exposure on blood pressure, negative affect, hostile social information processing, uncooperative behavior, and attitudes toward health risk behaviors among young men varying in lifetime violence exposure within the home and community. Experimental laboratory study. University campus situated within an urban environment. One hundred male undergraduates aged 18 to 21 years. Men who had previously reported differing amounts of lifetime home and community violence were randomly assigned to play The Simpsons: Hit and Run (low-violence condition) or Grand Theft Auto III (high-violence condition). Systolic and diastolic blood pressure; negative affect; hostile social information processing; uncooperative behavior; and permissive attitudes toward violence, alcohol use, marijuana use, and sexual activity without condom use. Men randomly assigned to play Grand Theft Auto III exhibited greater increases in diastolic blood pressure from a baseline rest period to game play, greater negative affect, more permissive attitudes toward using alcohol and marijuana, and more uncooperative behavior in comparison with men randomly assigned to play The Simpsons. Only among participants with greater exposure to home and community violence, play of Grand Theft Auto III led to elevated systolic blood pressure in comparison with play of The Simpsons (mean, 13 vs 5 mm Hg). Media violence exposure may play a role in the development of negative attitudes and behaviors related to health. Although youth growing up in violent homes and communities may become more physiologically aroused by media violence exposure, all youth appear to be at risk for potentially negative outcomes.

Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies.

PubMed

Ma, Jietao; Sun, Xin; Huang, Letian; Xiong, Zhicheng; Yuan, Meng; Zhang, Shuling; Han, Cheng-Bo

2016-01-01

Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. PubMed, Cochrane's Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55-1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors.

An evaluation of efficacy of balloon inflation on venous cannulation pain in children: a prospective, randomized, controlled study.

PubMed

Gupta, Devendra; Agarwal, Anil; Dhiraaj, Sanjay; Tandon, Manish; Kumar, Mukesh; Singh, Ravi Shankar; Singh, Prabhat K; Singh, Uttam

2006-05-01

Venipuncture is the most common painful event for a hospitalized child. We evaluated the efficacy of balloon inflation for attenuating venipuncture pain in children. Seventy-five pediatric patients aged 6-12 yr, ASA physical status I-II, of either sex, undergoing elective surgery were included in this prospective and randomized study. Patients were randomly divided into 3 equal groups of 25 each; Group I (control), Group II (distraction) pressed a rubber ball, and Group III (balloon) inflated a balloon. A manual venous occlusion was applied on the forearm and venipuncture was performed with a 22-gauge venous cannula. Pain was self-reported by a pain face scale with a 10-cm visual analog scale (VAS) placed at its back, where 0 = "no pain" and 10 = "worst imaginable pain." VAS scores of 1-3 were rated as mild, 4-6 as moderate, and >6 as severe. Median (interquartile range) VAS score in the balloon group was 1 (3), which was reduced as compared with 2 (2) and 4 (2) observed in the distraction and control groups, respectively (P < 0.000). Significant reduction in the incidence and severity of venipuncture pain was also observed in the balloon group compared with the other 2 groups (P < 0.05).

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2014-01-31

Agents October 01, 2013 through December 31, 2013 11 of 20 o S1203: A Randomized Phase III Study of Standard Cytarabine plus Daunorubicin (7+3...Therapy or Idarubicin with High Dose Cytarabine (IA) versus IA with Vorinostat (IA+V) in Younger Patients with Previously Untreated Acute Myeloid

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2013-10-30

under the following clinical trial protocol: o S1203: A Randomized Phase III Study of Standard Cytarabine plus Daunorubicin (7+3) Therapy or Idarubicin...with High Dose Cytarabine (IA) versus IA with Vorinostat (IA+V) in Younger Patients with Previously Untreated Acute Myeloid Leukemia (AML) o

Effect of paricalcitol on renin and albuminuria in non-diabetic stage III-IV chronic kidney disease: a randomized placebo-controlled trial

PubMed Central

2013-01-01

Background Vitamin D receptor activators reduce albuminuria, and may improve survival in chronic kidney disease (CKD). Animal studies suggest that these pleiotropic effects of vitamin D may be mediated by suppression of renin. However, randomized trials in humans have yet to establish this relationship. Methods In a randomized, placebo-controlled, double-blinded crossover study, the effect of oral paricalcitol (2 μg/day) was investigated in 26 patients with non-diabetic, albuminuric stage III-IV CKD. After treatment, plasma concentrations of renin (PRC), angiotensin II (AngII) and aldosterone (Aldo) were measured. GFR was determined by 51Cr-EDTA clearance. Assessment of renal NO dependency was performed by infusion of NG-monomethyl-L-arginine (L-NMMA). Albumin excretion rate (AER) was analyzed in 24-h urine and during 51Cr-EDTA clearance. Results Paricalcitol did not alter plasma levels of renin, AngII, Aldo, or urinary excretion of sodium and potassium. A modest reduction of borderline significance was observed in AER, and paricalcitol abrogated the albuminuric response to L-NMMA. Conclusions In this randomized, placebo-controlled trial paricalcitol only marginally decreased AER and did not alter circulating levels of renin, AngII or Aldo. The abrogation of the rise in albumin excretion by paricalcitol during NOS blockade may indicate that favourable modulation of renal NO dependency could be involved in mediating reno-protection and survival benefits in CKD. Trial registration ClinicalTrials.gov identifier: NCT01136564 PMID:23889806

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

PubMed Central

Judge, PK; Haynes, R; Herrington, WG; Storey, BC; Staplin, N; Bethel, A; Bowman, L; Brunskill, N; Cockwell, P; Dayanandan, R; Hill, M; Kalra, PA; McMurray, JJ; Taal, M; Wheeler, DC; Landray, MJ; Baigent, C; Baigent, C; Haynes, R; Landray, MJ; Dayanandan, R; Baxter, A; Staplin, N; Bethel, A; Bowman, L; Brunskill, N; Cockwell, P; Herrington, WG; Hill, M; Judge, PK; Kalra, PA; Knott, C; McMurray, JJ; Murphy, K; Taal, M; Wheeler, DC; Wheatley, K; Emberson, J; Tomson, C; Roderick, P

2017-01-01

Abstract Background Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. Methods UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor–neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin–angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. Results Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. Conclusions UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD. PMID:27646835

Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

PubMed

Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie; Corvol, Jean-Christophe; Schüpbach, Michael

2016-01-01

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. ClinicalTrials.gov NCT01341431.

Bee Venom for the Treatment of Parkinson Disease – A Randomized Controlled Clinical Trial

PubMed Central

Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie

2016-01-01

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. Trial Registration ClinicalTrials.gov NCT01341431 PMID:27403743

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review

PubMed Central

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Background Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. Data sources A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010–2015). Study eligibility criteria All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Intervention Quality of reporting was assessed using the Key Methodological Score. Results 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Limitations Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. Conclusions & implications of key findings This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles. PMID:29216190

Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.

PubMed

Baertsch, Marc-Andrea; Schlenzka, Jana; Mai, Elias K; Merz, Maximilian; Hillengaß, Jens; Raab, Marc S; Hose, Dirk; Wuchter, Patrick; Ho, Anthony D; Jauch, Anna; Hielscher, Thomas; Kunz, Christina; Luntz, Steffen; Klein, Stefan; Schmidt-Wolf, Ingo G H; Goerner, Martin; Schmidt-Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Salwender, Hans; Scheid, Christof; Nogai, Axel; Haenel, Mathias; Lindemann, Hans W; Martin, Hans; Noppeney, Richard; Weisel, Katja; Goldschmidt, Hartmut

2016-04-25

Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. ISRCTN16345835 (date of registration 2010-08-24).

Validation of the phase II feasibility study in a palliative care setting: gastrografin in malignant bowel obstruction.

PubMed

Lee, Cindy; Vather, Ryash; O'Callaghan, Anne; Robinson, Jackie; McLeod, Briar; Findlay, Michael; Bissett, Ian

2013-12-01

Malignant bowel obstruction (MBO) is common in patients with advanced cancer. To perform a phase II study to assess the feasibility of conducting a phase III trial investigating the therapeutic value of gastrografin in MBO. Randomized double-blinded placebo-controlled feasibility study. Participants received 100 mL of either gastrografin or placebo. Over 8 months, 57 patients were screened and 9 enrolled (15.8% recruitment rate). Of the 9 enrolled, 4 received gastrografin (with 2 completing assessment) and 5 received placebo (with 4 completing assessment). It is not feasible to conduct a phase III trial using the same study protocol. This study validates the use of the phase II feasibility study to assess protocol viability in a palliative population prior to embarking on a larger trial.

A randomized phase II/III trial of perioperative chemotherapy with adriamycin plus ifosfamide versus gemcitabine plus docetaxel for high-grade soft tissue sarcoma: Japan Clinical Oncology Group Study JCOG1306.

PubMed

Kataoka, Kozo; Tanaka, Kazuhiro; Mizusawa, Junki; Kimura, Aya; Hiraga, Hiroaki; Kawai, Akira; Matsunobu, Tomoya; Matsumine, Akihiko; Araki, Nobuhito; Oda, Yoshinao; Fukuda, Haruhiko; Iwamoto, Yukihide

2014-08-01

A randomized Phase II/III trial was planned to commence in March 2014. Perioperative chemotherapy with adriamycin plus ifosfamide is the current standard treatment for T2bN0M0 high-grade non-round cell soft tissue sarcoma. The purpose of this study is to confirm the non-inferiority of perioperative chemotherapy with gemcitabine and docetaxel to adriamycin plus ifosfamide for patients with T2bN0M0 or any TN1M0 non-round cell soft tissue sarcoma in the extremities and body wall. A total of 140 patients will be accrued from 28 Japanese institutions over 6 years. The primary endpoint in the Phase II part is the proportion of completion of pre-operative chemotherapy without progressive disease and overall survival in the Phase III part. The secondary endpoints are progression-free survival, response rate of pre-operative chemotherapy, pathological response rate, proportion of preservation of diseased limbs, disease control rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000013175 [http://www.umin.ac.jp/ctr/index.htm]. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Perioperative Hydrocortisone Reduces Major Complications After Pancreaticoduodenectomy: A Randomized Controlled Trial.

PubMed

Laaninen, Matias; Sand, Juhani; Nordback, Isto; Vasama, Kaija; Laukkarinen, Johanna

2016-11-01

The aim of this study was to study whether post-pancreaticoduodenectomy complications (PPDC) in high-risk patients can be reduced with hydrocortisone. Soft pancreas is a well-known risk factor for PPDC. Previously, we have shown that patients with >40% acini in the pancreatic transection line are most prone to PPDC. Recent studies have demonstrated that surgical trauma leads to inflammation of the pancreatic remnant, which precedes PPDC. On the basis of power analysis, randomized controlled trial (RCT) (Clinicaltrials.gov NCT01460615), 155 patients (February 2011-May 2015) scheduled for pancreaticoduodenectomy were randomized to intravenous (i.v.) treatment with hydrocortisone 100 mg or placebo. All patients received the first dose at the induction of anesthesia. During the operation, the percentage of acini was calculated from pancreatic transection line frozen samples by a pathologist. As planned, only the high-risk patients with >40% acini (n = 62) continued in the study to receive in total 8 doses of randomization-based hydrocortisone/placebo every 8 hours. Primary endpoints were urine trypsinogen positive days and overall complications (Clavien-Dindo III-IV). Postoperative pancreatic fistulas (POPFs), postpancreatectomy hemorrhage (PPH), and delayed gastric emptying (DGE) were also graded. Hydrocortisone treatment did not alter trypsinogen release (2 or more positive days 46% vs 50%), but it significantly reduced overall complications compared with placebo in the high-risk patients (18% vs 41%; P < 0.05; Clavien-Dindo III-IV). Also, clinically significant POPF (11% vs 27%), PPH (14% vs 24%), and DGE (29% vs 44%) tended to be lower in the hydrocortisone group. Ninety-day mortality was zero. This RCT shows that in high-risk patients, overall PPDC can be significantly reduced with hydrocortisone treatment. Inflammation may be an important mediator of PPDC.

A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease.

PubMed

Ostrowitzki, Susanne; Lasser, Robert A; Dorflinger, Ernest; Scheltens, Philip; Barkhof, Frederik; Nikolcheva, Tania; Ashford, Elizabeth; Retout, Sylvie; Hofmann, Carsten; Delmar, Paul; Klein, Gregory; Andjelkovic, Mirjana; Dubois, Bruno; Boada, Mercè; Blennow, Kaj; Santarelli, Luca; Fontoura, Paulo

2017-12-08

Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β (Aβ) and removes Aβ plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer's disease (AD). In this randomized, double-blind, placebo-controlled phase III study, we investigated gantenerumab over 2 years. Patients were randomized to gantenerumab 105 mg or 225 mg or placebo every 4 weeks by subcutaneous injection. The primary endpoint was the change from baseline to week 104 in Clinical Dementia Rating Sum of Boxes (CDR-SB) score. We evaluated treatment effects on cerebrospinal fluid biomarkers (all patients) and amyloid positron emission tomography (substudy). A futility analysis was performed once 50% of patients completed 2 years of treatment. Safety was assessed in patients who received at least one dose. Of the 3089 patients screened, 797 were randomized. The study was halted early for futility; dosing was discontinued; and the study was unblinded. No differences between groups in the primary (least squares mean [95% CI] CDR-SB change from baseline 1.60 [1.28, 1.91], 1.69 [1.37, 2.01], and 1.73 [1.42, 2.04] for placebo, gantenerumab 105 mg, and gantenerumab 225 mg, respectively) or secondary clinical endpoints were observed. The incidence of generally asymptomatic amyloid-related imaging abnormalities increased in a dose- and APOE ε4 genotype-dependent manner. Exploratory analyses suggested a dose-dependent drug effect on clinical and biomarker endpoints. The study was stopped early for futility, but dose-dependent effects observed in exploratory analyses on select clinical and biomarker endpoints suggest that higher dosing with gantenerumab may be necessary to achieve clinical efficacy. ClinicalTrials.gov, NCT01224106 . Registered on October 14, 2010.

Challenges of conducting a prospective clinical trial for older patients: Lessons learned from NCCTG N0949 (alliance).

PubMed

McCleary, Nadine J; Hubbard, Joleen; Mahoney, Michelle R; Meyerhardt, Jeffrey A; Sargent, Daniel; Venook, Alan; Grothey, Axel

2018-01-01

While the risk of developing colorectal cancer increases with age, there are limited prospective data regarding best treatment in the older adult population. We launched a phase III trial to evaluate difference in treatment outcome for older adults (aged ≥70years) with advanced colorectal cancer. Here we review the challenges faced and reasons for poor accrual to N0949. We describe the conceptualization, development and limited results of N0949, a randomized phase III study of fluoropyrimidine/bevacizumab with or without oxaliplatin (mFOLFOX7 or XELOX) as first line chemotherapy for metastatic colorectal cancer. Fluoropyrimidine was physician choice (e.g., 5-FU/LV or capecitabine). Of the projected 380 patients, only 32 patients were enrolled between the study activation in January 2011 until its closure in September 2012. Reasons for poor accrual included eligibility criteria that were too stringent, discomfort with randomizing older patients to regimens of varying intensity without considering their physical fitness, and discomfort with the use of bevacizumab in the older patient population. Several efforts were mounted to design a rationale and age-appropriate study, consider toxicities and varying study practices, and be responsive to stakeholder feedback. Challenges were experienced in conducting the first prospective phase III study evaluating progression-free survival of older adults with advanced colorectal cancer receiving palliative chemotherapy with fluoropyrimidine/bevacizumab with or without oxaliplatin in the USA. Future efforts to evaluate treatment outcomes in the older adult population should reflect on lessons learned in this large national effort. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficiency of compensatory orthodontic treatment of mild Class III malocclusion with two different bracket systems

PubMed Central

Aragón, Mônica L. C.; Bichara, Lívia M.; Flores-Mir, Carlos; Almeida, Guilherme; Normando, David

2017-01-01

ABSTRACT Objective: The purpose of this study was to assess the efficiency of compensatory orthodontic treatment of patients with mild Class III malocclusion with two preadjusted bracket systems. Method: Fifty-six matched patients consecutively treated for mild Class III malocclusion through compensatory dentoalveolar movements were retrospectively evaluated after analysis of orthodontic records. The sample was divided into two groups according to the brackets used: Group 1 = non-Class III compensated preadjusted brackets, Roth prescription (n = 28); Group 2 = compensated Class III preadjusted brackets, Capelozza III prescription (n = 28). Cephalometric analysis, number of appointments and missed appointments, months using Class III elastics, and bond/band failures were considered. Treatment time, Peer Assessment Rating (PAR) index at the beginning (PAR T1) and end of treatment (PAR T2) were used to calculate treatment efficiency. Comparison was performed using a MANOVA at p< 0.05. Results: Missed appointments, bond or band failures, number of months using the Class III intermaxillary elastics, and cephalometric measurements showed no statistically significant difference (p> 0.05) between groups. Patients treated with Roth brackets had a treatment time 7 months longer (p= 0.01). Significant improvement in the patient’s occlusion (PAR T2-T1) was observed for both groups without difference (p= 0.22). Conclusions: Orthodontic brackets designed for compensation of mild Class III malocclusions appear to be more efficient than non-compensated straight-wire prescription brackets. Treatment time for Class III patients treated with brackets designed for compensation was shorter than with Roth prescription and no difference in the quality of the occlusal outcome was observed. A prospective randomized study is suggested to provide a deeper look into this subject. PMID:29364379

Needful Implements in Improving the Study and Scholastic Skills of Nigerian Secondary School Students

ERIC Educational Resources Information Center

Adegoroye, Biodun-Smith; Ajagbe, Adesina Adunfe

2015-01-01

Showing concern about the consistent depreciation in expected study and scholastic behaviours among Secondary School students and the trailing failure in school test and exams and public exams, the authors gathered empirical report on the chosen variables among a randomly selected 1,200 secondary school students in JSS I, II, III, SSS I, II, III…

A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

PubMed

Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L

2007-09-01

Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

[Development of an orphan drug to treat a genetic disease: the paradigm of agalsidase beta].

PubMed

Germain, Dominique P; Benistan, Karelle

2007-03-01

Preclinical and phase I/II studies gave the proof of principle of enzyme replacement therapy (ERT) with recombinant alpha-galactosidase A through the demonstration of the clearance of the accumulated subtrate from plasma and tissues. In a multicenter, randomized, placebo-controlled, double-blind phase Ill study, the biological efficacy of recombinant alpha-galactosidose A (agalsidase beta 1 mg/kg/714 days) was demonstrated on the basis of complete clearance of accumulated globotriaosylceramide from the endothelia of the kidney, heart and skin. The phase III extension study data gives additional results: kidney function appears to be stabilized after 54 to 60 months of treatment with agolsidase beta in most patients. Intent-to-treat analysis of a double-blind, randomized, placebo-controlled, phase IV study, showed that, adjusted for on imbalance in baseline proteinuria, agalsidase beta significantly reduces by 53% the risk of a first clinical event (renal, cardiac and cerebrovascular), compared with placebo. Clinical benefits of ERT depend on patients' clinical status at baseline, therefore prompting for onset of ERT before irreversible damage occur and underlying the need to stratify patients' populations to better understand the outcome of ERT.

Once-daily USL255 as adjunctive treatment of partial-onset seizures: Randomized phase III study

PubMed Central

Chung, Steve S; Fakhoury, Toufic A; Hogan, R Edward; Nagaraddi, Venkatesh N; Blatt, Ilan; Lawson, Balduin; Arnold, Stephan; Anders, Bob; Clark, Annie M; Laine, Dawn; Meadows, R Shawn; Halvorsen, Mark B

2014-01-01

Objective To evaluate the efficacy and safety of USL255, Qudexy™ XR (topiramate) extended-release capsules, as an adjunctive treatment for refractory partial-onset seizures (POS) in adults taking one to three concomitant antiepileptic drugs. Methods In this global phase III study (PREVAIL; NCT01142193), 249 adults with POS were randomized 1:1 to once-daily USL255 (200 mg/day) or placebo. The primary and key secondary efficacy endpoints were median percent reduction in weekly POS frequency and responder rate (proportion of patients with ≥50% reduction in seizure frequency). Seizure freedom was also assessed. Safety (adverse events, clinical and laboratory findings), as well as treatment effects on quality of life (QOLIE-31-P) and clinical global impression of change (CGI-C), were evaluated. Results Across the entire 11-week treatment phase, USL255 significantly reduced the median percent seizure frequency and significantly improved responder rate compared with placebo. Efficacy over placebo was observed early in treatment, in patients with highly refractory POS, and in those with the most debilitating seizure types (i.e., complex partial, partial secondarily generalized). USL255 was safe and generally well tolerated with a low incidence of neurocognitive adverse events. USL255 was associated with significant clinical improvement without adversely affecting quality of life. Significance The PREVAIL phase III clinical study demonstrated that once-daily USL255 (200 mg/day) significantly improved seizure control and was safe and generally well tolerated with few neurocognitive side effects. PMID:24902983

The prevalence of metabolic syndrome according to various definitions and hypertriglyceridemic-waist in malaysian adults.

PubMed

Zainuddin, Laila Ruwaida Mohd; Isa, Nurfirdaus; Muda, Wan Manan Wan; Mohamed, Hamid Jan

2011-10-01

Metabolic syndrome can be diagnosed according to several different criteria such as the latest International Diabetes Federation (IDF), National Cholesterol Education Program Adult Treatment Program III (NCEP ATPIII), and World Health Organization (WHO). The objectives of this study were to determine the prevalence of metabolic syndrome and the concordance between the above mentioned definition, and hypertriglyceridemic-waist criteria. This cross sectional study was done in Bachok, Malaysia and involved 298 respondents aged between 18 to 70 years. Multistage random sampling method was used to identify study locations while convenient random sampling method was applied to select individuals. Hypertriglyceridemic waist was defined from an internationally acceptable cut-off criterion. Kappa statistic (κ test) was used to determine the concordance between various definitions and hypertriglyceridemic-waist. The prevalence of metabolic syndrome based on different definitions was 32.2% (IDF), 28.5% (NCEP ATP III) and 12.4% (modified WHO). The prevalence of hypertriglyceridemic-waist was 19.7% and based on the IDF criteria a total of 97.5% participants with hypertriglyceridemic-waist had metabolic syndrome. The IDF criteria showed the highest concordance with NCEP ATPIII criteria (κ = 0.63), followed by hypertriglyceridemic-waist criteria (κ = 0.62) and WHO criteria (κ = 0.26). The prevalence of metabolic syndrome was highest using the IDF criteria compared to NCEP ATPIII, modified WHO and hypertriglyceridemic-waist. There was a good concordance of IDF criteria with NCEP ATP III and hypertriglyceridemic-waist criteria.

A phase III study evaluating oral glutamine and transforming growth factor-beta 2 on chemotherapy-induced toxicity in patients with digestive neoplasm.

PubMed

Khemissa, Faïza; Mineur, Laurent; Amsellem, Caroline; Assenat, Eric; Ramdani, Mohamed; Bachmann, Patrick; Janiszewski, Chloé; Cristiani, Isabelle; Collin, Fideline; Courraud, Julie; de Forges, Hélène; Dechelotte, Pierre; Senesse, Pierre

2016-03-01

Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities. The primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-β2 (TGF-β2) in the prevention of grade 3-4 non-hematological toxicities induced by chemotherapy in patients with GI cancer. We designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect(®) (CP) or a control isocaloric diet (without TGF-β2 or glutamine). Between November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3-4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3-4 hematological toxicities or reasons for treatment interruption. This randomized study does not support the hypothesis that oral glutamine and TGF-β2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Everolimus for the Treatment of Advanced Pancreatic Neuroendocrine Tumors: Overall Survival and Circulating Biomarkers From the Randomized, Phase III RADIANT-3 Study.

PubMed

Yao, James C; Pavel, Marianne; Lombard-Bohas, Catherine; Van Cutsem, Eric; Voi, Maurizio; Brandt, Ulrike; He, Wei; Chen, David; Capdevila, Jaume; de Vries, Elisabeth G E; Tomassetti, Paola; Hobday, Timothy; Pommier, Rodney; Öberg, Kjell

2016-11-10

Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to open-label everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intent-to-treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.

Evaluation of rotigotine transdermal patch for the treatment of depressive symptoms in patients with Parkinson's disease.

PubMed

Chung, Sun Ju; Asgharnejad, Mahnaz; Bauer, Lars; Ramirez, Francisco; Jeon, Beomseok

2016-08-01

To evaluate the dopamine receptor agonist, rotigotine, for improving depressive symptoms in patients with Parkinson's disease (PD). Patients were randomized 1:1 to rotigotine or placebo, titrated for ≤7 weeks, and maintained at optimal/maximum dose for 8-weeks. Primary efficacy variable: 17- item Hamilton Depression Rating Scale (HAM-D 17) total score change from baseline to end-of-maintenance. Secondary variables: changes in Beck Depression Inventory-II, Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living [ADL]) and III (motor) subscores, UPDRS II+III total, patient-rated Apathy Scale (AS), and Snaith-Hamilton Pleasure Scale. Of 380 patients randomized, 149/184 (81.0%) rotigotine-treated and 164/196 (83.7%) placebo-treated patients completed the study. mean (±SD) age 65.2 (±8.5) years; time since PD-diagnosis 2.74 (±3.08) years; 42.6% male. The treatment difference (LS mean [95% CI]) in change from baseline HAM-D 17 was -1.12 (-2.56, 0.33; p = 0.1286). UPDRS II, III, II+III and AS scores improved numerically with rotigotine versus placebo. Common adverse events with higher incidence with rotigotine: nausea, application/instillation site reactions, vomiting, and pruritus. Forty-one (10.8%) patients discontinued owing to adverse events (25 rotigotine/16 placebo). No statistically significant improvement in depressive symptoms were observed with rotigotine versus placebo. ADL, motor function, and patient-rated apathy improved numerically. ClinicalTrials.gov: NCT01523301.

Knowledge, Affection and Basic Attitudes Toward Animals in American Society. Phase III.

ERIC Educational Resources Information Center

Kellert, Stephen R.; Berry, Joyce K.

This paper, third in a series of five reports on results of a national study of American attitudes, knowledge, and behaviors toward wildlife and natural habitats, focuses on the American public's attitudes, perceptions, and understanding of animals. Data were derived from questionnaires administered to 3,107 randomly selected Americans (18 years…

Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies

PubMed Central

Ma, Jietao; Sun, Xin; Huang, Letian; Xiong, Zhicheng; Yuan, Meng; Zhang, Shuling; Han, Cheng-Bo

2016-01-01

Background Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. Methods PubMed, Cochrane’s Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. Results Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55–1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. Conclusion Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors. PMID:27524907

Randomness increases self-reported anxiety and neurophysiological correlates of performance monitoring

PubMed Central

Kay, Aaron C.; Inzlicht, Michael

2015-01-01

Several prominent theories spanning clinical, social and developmental psychology suggest that people are motivated to see the world as a sensible orderly place. These theories presuppose that randomness is aversive because it is associated with unpredictability. If this is the case, thinking that the world is random should lead to increased anxiety and heightened monitoring of one’s actions and their consequences. Here, we conduct experimental tests of both of these ideas. Participants read one of three passages: (i) comprehensible order, (ii) incomprehensible order and (iii) randomness. In Study 1, we examined the effects of these passages on self-reported anxiety. In Study 2, we examined the effects of the same manipulation on the error-related negativity (ERN), an event-related brain potential associated with performance monitoring. We found that messages about randomness increased self-reported anxiety and ERN amplitude relative to comprehensible order, whereas incomprehensible order had intermediate effects. These results lend support to the theoretically important idea that randomness is unsettling because it implies that the world is unpredictable. PMID:25062840

Power of an Adaptive Trial Design for Endovascular Stroke Studies: Simulations Using IMS (Interventional Management of Stroke) III Data.

PubMed

Lansberg, Maarten G; Bhat, Ninad S; Yeatts, Sharon D; Palesch, Yuko Y; Broderick, Joseph P; Albers, Gregory W; Lai, Tze L; Lavori, Philip W

2016-12-01

Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies. We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design. The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%). These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern. © 2016 American Heart Association, Inc.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review.

PubMed

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010-2015). All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Quality of reporting was assessed using the Key Methodological Score. 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine.

PubMed

Demetri, George D; Schöffski, Patrick; Grignani, Giovanni; Blay, Jean-Yves; Maki, Robert G; Van Tine, Brian A; Alcindor, Thierry; Jones, Robin L; D'Adamo, David R; Guo, Matthew; Chawla, Sant

2017-10-20

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m 2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m 2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.

Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

PubMed

Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

2016-01-01

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

Post dural puncture headache after spinal anaesthesia for caesarean section: a comparison of 25 g Quincke, 27 g Quincke and 27 g Whitacre spinal needles.

PubMed

Shaikh, Jan Muhammad; Memon, Amna; Memon, Muhammad Ali; Khan, Majida

2008-01-01

To compare the frequency and severity of post dural puncture headache in obstetric patients using 25G Quincke, 27G Quincke and 27G Whitacre spinal needles. Comparative, randomized, double-blind, interventional study. Liaquat University Hospital Hyderabad from October 2005 to December 2006. 480 ASA I-II full term pregnant women, 18 to 45 years of age, scheduled for elective Caesarean section, under spinal anaesthesia, were randomized into three groups: Group I (25G Quincke spinal needle: n=168), Group II (27G Quincke spinal needle: n=160) and Group III (27G Whitacre spinal needle: n=152). Spinal anaesthesia was performed with 1.5-2.0 ml 0.75% hyperbaric bupivacaine using 25G Quincke spinal needle (Group I), 27G Quincke spinal needle (Group II) and 27G Whitacre spinal needle (Group III) at L3-4 inter-vertebral space. Each patient was assessed daily for four consecutive days following Caesarean section. Frequency and severity and of postdural puncture headache (PDPH) were recorded. Data were analyzed using SPSS-11. Frequency of PDPH following the use of 25G Quincke (Group I), 27G Quincke (Group II) and 27G Whitacre (Group III) spinal needles was 8.3% (14/168), 3.8% (6/160) and 2.0% (3/152) respectively. In Group I, PDPH was mild in 5 patients, moderate in 7 patients and severe in 2 patients. In Group II, it was mild in 2, moderate in 3 and severe in 1 patient. In group III, it was mild in 2 and moderate in 1 patient. Severe PDPH did not occur in Group III. Most of the patients with PDPH developed it on 1st and 2nd postoperative day. When using a 27G Whitacre spinal needle, the frequency and severity of PDPH was significantly lower than when a 25G Quincke or 27G Quincke needle was used.

No evidence for [O III] variability in Mrk 142

NASA Astrophysics Data System (ADS)

Barth, Aaron J.; Bentz, Misty C.

2016-05-01

Using archival data from the 2008 Lick AGN Monitoring Project, Zhang & Feng claimed to find evidence for flux variations in the narrow [O III] emission of the Seyfert 1 galaxy Mrk 142 over a two-month time span. If correct, this would imply a surprisingly compact size for the narrow-line region. We show that the claimed [O III] variations are merely the result of random errors in the overall flux calibration of the spectra. The data do not provide any support for the hypothesis that the [O III] flux was variable during the 2008 monitoring period.

Millon Clinical Multiaxial Inventory-III Subtypes of Opioid Dependence: Validity and Matching to Behavioral Therapies

ERIC Educational Resources Information Center

Ball, Samuel A.; Nich, Charla; Rounsaville, Bruce J.; Eagan, Dorothy; Carroll, Kathleen M.

2004-01-01

The concurrent and predictive validity of 2 different methods of Millon Clinical Multiaxial Inventory-III subtyping (protocol sorting, cluster analysis) was evaluated in 125 recently detoxified opioid-dependent outpatients in a 12-week randomized clinical trial. Participants received naltrexone and relapse prevention group counseling and were…

Melanoma.

PubMed

Gershenwald, J E

2001-01-01

The presentations at the American Society of Clinical Oncology 2001 meeting reported or updated the results of phase I, II, and III randomized trials and also reported important meta-analyses and retrospective studies impacting on the management of patients with melanoma. In the treatment of early stage melanoma, the prognostic significance of pathologic status of sentinel lymph nodes was affirmed. With respect to regional nodal involvement (American Joint Committee on Cancer [AJCC] stage III), investigators presented the interim results of the United Kingdom randomized low-dose interferon (IFN) trial, and up-to-date meta-analyses of several IFN trials including a pooled analysis of the Eastern Cooperative Oncology Group trials evaluating interferon in the adjuvant setting. In the advanced disease setting (AJCC stage IV), several studies elucidated the pros and cons of biochemotherapy in patients with metastatic melanoma, with an emphasis on seeking to improve response in the central nervous system and durability of response in general. Thought provoking was new data regarding the potential for lovastatin to act as a chemopreventive agent for melanoma. Translational studies were presented, one supporting the importance of HLA-typing in developing targeted vaccine therapy. Finally, the results of a novel experimental melanoma vaccine were presented using autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96).

Moving Beyond Conventional Clinical Trial End Points in Treatment-refractory Metastatic Colorectal Cancer: A Composite Quality-of-life and Symptom Control End Point.

PubMed

Gong, Jun; Wu, Daniel; Chuang, Jeremy; Tuli, Richard; Simard, John; Hendifar, Andrew

2017-11-01

This review highlights the evidence supporting symptom control and quality-of-life (QOL) measures as predictors of survival in treatment-refractory metastatic colorectal cancer (mCRC) and describes a composite symptom control and QOL end point recently reported in a Phase III trial that may serve as a more reasonable end point of efficacy in this population. A literature search was conducted using MEDLINE to identify clinical studies (including case series and observational, retrospective, and prospective studies) that reported the predictive value of QOL measures for survival in mCRC. The search was limited by the following key words: quality of life, survival, and colorectal cancer. We then performed a second search limited to studies of randomized and Phase III design in mCRC to identify studies that used QOL assessments as their primary end points. A manual search was also performed to include additional studies of potential relevance. There is increasing evidence to support that symptom control and QOL measures are predictors of survival in treatment-refractory mCRC and can serve as an alternative but equally as important end point to survival in this population. A recent large, randomized Phase III trial using a composite primary end point of lean body mass, pain, anorexia, and fatigue reported the feasibility in evaluating benefit in mCRC beyond conventional clinical trial end points. Future studies in treatment-refractory mCRC may be better served by evaluating improvement in symptom control and QOL, which may otherwise serve as the best predictor of survival in last-line treatment settings. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Analysis of Regional Timelines To Set Up a Global Phase III Clinical Trial in Breast Cancer: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Experience

PubMed Central

de Azambuja, Evandro; Bradbury, Ian; Saini, Kamal S.; Bines, José; Simon, Sergio D.; Dooren, Veerle Van; Aktan, Gursel; Pritchard, Kathleen I.; Wolff, Antonio C.; Smith, Ian; Jackisch, Christian; Lang, Istvan; Untch, Michael; Boyle, Frances; Xu, Binghe; Baselga, Jose; Perez, Edith A.; Piccart-Gebhart, Martine

2013-01-01

Purpose. This study measured the time taken for setting up the different facets of Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), an international phase III study being conducted in 44 participating countries. Methods. Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank's criteria. Results. South America had a significantly longer time to RA approval (median: 236 days, range: 21–257 days) than Europe (median: 52 days, range: 0–151 days), North America (median: 26 days, range: 22–30 days), and Asia-Pacific (median: 62 days, range: 37–75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21–257 days) than high-income (median: 47 days, range: 0–112 days) and lower-middle income economies (median: 57 days, range: 37–62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0–174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26–412 days). Conclusion. This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research. PMID:23359433

In vitro microleakage of glass-ionomer composite resin hybrid materials.

PubMed

Rodrigues, J A; De Magalhães, C S; Serra, M C; Rodrigues Júnior, A L

1999-01-01

The purpose of this study was to evaluate the microleakage of six glass-ionomer composite resin hybrid materials compared with a glass-ionomer cement and a composite resin. Standardized class 5 dentin cavities were prepared on root surfaces of 240 extracted human teeth that were randomly assigned to eight groups and restored using the following restorative systems: (I) Vitremer, (II) Compoglass, (III) Photac-Fil Aplicap, (IV) Variglass, (V) Dyract, (VI) Fuji II LC, (VII) Ketac-Fil Aplicap, and (VIII) Z100. The teeth were thermocycled, placed in a 2% methylene blue solution, and sectioned with diamond disks. Dye penetration was scored on a scale of 0-3. Results showed no significant differences among groups VIII, IV, I, V, VI, III, and II. There were also no significant differences among groups VI, III, II, and VII.

Predictors of employment status of treated patients with DSM-III-R diagnosis. Can logistic regression model find a solution?

PubMed

Daradkeh, T K; Karim, L

1994-01-01

To investigate the predictors of employment status of patients with DSM-III-R diagnosis, 55 patients were selected by a simple random technique from the main psychiatric clinic in Al Ain, United Arab Emirates. Structured and formal assessments were carried out to extract the potential predictors of outcome of schizophrenia. Logistic regression model revealed that being married, absence of schizoid personality, free or with minimum symptoms of the illness, later age of onset, and higher educational attainment were the most significant predictors of employment outcome. The implications of the results of this study are discussed in the text.

Meta-analysis of surgical strategies in perforated left colonic diverticulitis with generalized peritonitis.

PubMed

Schmidt, Sina; Ismail, Tarek; Puhan, Milo A; Soll, Christopher; Breitenstein, Stefan

2018-06-01

Surgical strategies for perforated diverticulitis (Hinchey stages III and IV) remain controversial. This systematic review aimed to compare the outcome of primary anastomosis, Hartmann procedure and laparoscopic lavage. A systematic literature search was conducted through Medline, Embase, Cochrane Central Register and Health Technology Assessment Database to identify randomized and non-randomized controlled trials involving patients with perforated left-sided colonic diverticulitis comparing different surgical strategies. The methodological quality of the included studies was assessed systematically (Grading of Recommendations, Assessment, Development and Evaluation) and a meta-analysis was performed. After screening 4090 titles and abstracts published between 1958 and January 2018, 148 were selected for full text assessment. Sixteen trials (7 RCTs, 9 non-RCTs) with 1223 patients were included. Mortality rates were not significantly different between Hartmann procedure and primary anastomosis for Hinchey III and IV, neither in the meta-analysis of three RCTs (RR 2.03 (95% CI 0.79 to 5.25); p = 0.14, moderate quality of evidence) nor in the meta-analysis of six observational studies (RR 1.53 (95% CI 0.89 to 2.65); p = 0.13, very low quality of evidence). However, stoma reversal rates were significantly higher in the primary anastomosis group (RR 0.73 (95% CI 0.58 to 0.98); p = 0.008, moderate quality of evidence). Meta-analysis of four RCTs showed no significant difference between laparoscopic lavage for Hinchey III compared to sigmoid resection neither for mortality (RR 1.07 (95% CI 0.65 to 1.76); p = 0.79, moderate quality of evidence) nor for major complications (RR 0.86 (95% CI 0.69 to 1.08); p = 0.20, moderate quality of evidence). This systematic review suggests similar rates of complications but higher rates of colonic restoration after primary anastomosis compared to Hartmann procedure in perforated diverticulitis with generalized peritonitis (Hinchey III and IV). Results in laparoscopic lavage for Hinchey III are not superior to primary resection. However, further studies with a careful interpretation of the meaning of re-interventions are required.

A single-blinded, randomized, parallel group superiority trial investigating the effects of footwear and custom foot orthoses versus footwear alone in individuals with patellofemoral joint osteoarthritis: a phase II pilot trial protocol.

PubMed

Wyndow, Narelle; Crossley, Kay M; Vicenzino, Bill; Tucker, Kylie; Collins, Natalie J

2017-01-01

Patellofemoral joint osteoarthritis is a common condition, yet information regarding conservative management is lacking. Foot orthoses are an effective intervention for improving pain and function in younger individuals with patellofemoral pain and may be effective in those with patellofemoral osteoarthritis. This pilot study will seek to establish the feasibility of a phase III randomised controlled trial to investigate whether foot orthoses worn in prescribed motion controlled footwear are superior to prescribed motion control footwear alone in the management of patellofemoral osteoarthritis. This phase II pilot clinical trial is designed as a randomized, single-blind, parallel group, two arm, superiority trial. The trial will recruit 44 participants from Queensland and Tasmania, Australia. Volunteers aged 40 years and over must have clinical symptoms and radiographic evidence of patellofemoral osteoarthritis to be eligible for inclusion. Those eligible will be randomized to receive either foot orthoses and prescribed motion control shoes, or prescribed motion control shoes alone, to be worn for a period of 4 months. The feasibility of a phase III clinical trial will be evaluated by assessing factors such as recruitment rate, number of eligible participants, participant compliance with the study protocol, adverse events, and drop-out rate. A secondary aim of the study will be to determine completion rates and calculate effect sizes for patient reported outcome measures such as knee-related symptoms, function, quality of life, kinesiophobia, self-efficacy, general and mental health, and physical activity at 2 and 4 months. Primary outcomes will be reported descriptively while effect sizes and 95% confidence intervals will be calculated for the secondary outcome measures. Data will be analysed using an intention-to-treat principle. The results of this pilot trial will help determine the feasibility of a phase III clinical trial investigating whether foot orthoses plus motion control footwear are superior to motion control footwear alone in individuals with patellofemoral osteoarthritis. A Phase III clinical trial will help guide footwear and foot orthoses recommendations in the clinical management of this disorder. Retrospectively registered with the Australian New Zealand Clinical Trials Registry: ACTRN12615000002583. Date registered: 07/01/15.

Eastern Kentucky Teacher and Administrative Stress: Part III

ERIC Educational Resources Information Center

Wright, Sam; Ballestero, Victor

2012-01-01

The purpose of this research was to survey randomly selected Eastern Kentucky Superintendents to collect data about stress in public schools. This was the third year of a continuation study for Eastern Kentucky that collected data on how men and women teachers and men and women administrators handle stress. A stress survey (Appendix A) was sent to…

Effects of feeding monensin to bred heifers fed in a drylot on nutrient and energy balance

USDA-ARS?s Scientific Manuscript database

The objective of this study was to determine if feeding monensin would improve diet digestion, energy and nitrogen balance in bred heifers receiving a limit-fed corn stalk-based diet. Sixteen pregnant Meat Animal Research Center (MARC) III composite heifers were used in a 161 d completely randomized...

A comparison of numerical solutions of partial differential equations with probabilistic and possibilistic parameters for the quantification of uncertainty in subsurface solute transport.

PubMed

Zhang, Kejiang; Achari, Gopal; Li, Hua

2009-11-03

Traditionally, uncertainty in parameters are represented as probabilistic distributions and incorporated into groundwater flow and contaminant transport models. With the advent of newer uncertainty theories, it is now understood that stochastic methods cannot properly represent non random uncertainties. In the groundwater flow and contaminant transport equations, uncertainty in some parameters may be random, whereas those of others may be non random. The objective of this paper is to develop a fuzzy-stochastic partial differential equation (FSPDE) model to simulate conditions where both random and non random uncertainties are involved in groundwater flow and solute transport. Three potential solution techniques namely, (a) transforming a probability distribution to a possibility distribution (Method I) then a FSPDE becomes a fuzzy partial differential equation (FPDE), (b) transforming a possibility distribution to a probability distribution (Method II) and then a FSPDE becomes a stochastic partial differential equation (SPDE), and (c) the combination of Monte Carlo methods and FPDE solution techniques (Method III) are proposed and compared. The effects of these three methods on the predictive results are investigated by using two case studies. The results show that the predictions obtained from Method II is a specific case of that got from Method I. When an exact probabilistic result is needed, Method II is suggested. As the loss or gain of information during a probability-possibility (or vice versa) transformation cannot be quantified, their influences on the predictive results is not known. Thus, Method III should probably be preferred for risk assessments.

The effect of platelet-rich plasma on clinical outcomes in lateral epicondylitis.

PubMed

Ahmad, Zafar; Brooks, Roger; Kang, Sertaz-Niel; Weaver, Holly; Nunney, Ian; Tytherleigh-Strong, Graham; Rushton, Neil

2013-11-01

To evaluate the evidence for application of platelet-rich plasma (PRP) in lateral epicondylitis. We carried out a systematic review of the current evidence on the effects of PRP in lateral epicondylitis on clinical outcomes. We performed a comprehensive search of the PubMed, Medline, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Embase databases using various combinations of the commercial names of each PRP preparation and "lateral epicondylitis" (with its associated terms), looking specifically at human studies. Data validity was assessed and collected on clinical outcome. Nine studies met the inclusion criteria, of which 5 were randomized controlled trials. Two cohort studies showed that PRP improved clinical satisfaction scores. One case-control study showed that PRP yielded a significantly greater improvement in symptoms compared with bupivacaine. Two randomized controlled trials compared the effect of injections of PRP and blood. Only 1 of the studies noted a significant difference at the 6-week time point. Three randomized controlled trials compared corticosteroids with PRP. Two of the smaller trials, which had follow-up periods of 6 weeks and 3 months, showed no significant difference between treatment groups. The largest randomized controlled trial found that PRP had significant benefit compared with corticosteroids with regard to pain and Disabilities of the Arm, Shoulder and Hand scores at 1- and 2-year time points. This review highlights the limited but evolving evidence for the use of PRP in lateral epicondylitis; however, further research is required to understand the concentration and preparation that facilitate the best clinical outcome. Characterizing the timing of the intervention would optimize the health economics behind the decision to treat for the patient and health care provider. Level III, systematic review of Level I to III studies. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Comparative effectiveness and cost-effectiveness of Chuna manual therapy versus conventional usual care for nonacute low back pain: study protocol for a pilot multicenter, pragmatic randomized controlled trial (pCRN study).

PubMed

Shin, Byung-Cheul; Kim, Me-Riong; Cho, Jae-Heung; Jung, Jae-Young; Kim, Koh-Woon; Lee, Jun-Hwan; Nam, Kibong; Lee, Min Ho; Hwang, Eui-Hyoung; Heo, Kwang-Ho; Kim, Namkwen; Ha, In-Hyuk

2017-01-17

While Chuna manual therapy is a Korean manual therapy widely used primarily for low back pain (LBP)-related disorders in Korea, well-designed studies on the comparative effectiveness of Chuna manual therapy are scarce. This study is the protocol for a three-armed, multicenter, pragmatic randomized controlled pilot trial. Sixty severe nonacute LBP patients (pain duration of at least 3 weeks, Numeric Rating Scale (NRS) ≥5) will be recruited at four Korean medicine hospitals. Participants will be randomly allocated to the Chuna group (n = 20), usual care group (n = 20), or Chuna plus usual care group (n = 20) for 6 weeks of treatment. Usual care will consist of orally administered conventional medicine, physical therapy, and back pain care education. The trial will be conducted with outcome assessor and statistician blinding. The primary endpoint will be NRS of LBP at week 7 post randomization. Secondary outcomes include NRS of leg pain, the Oswestry Disability Index (ODI), the Patient Global Impression of Change (PGIC), the Credibility and Expectancy Questionnaire, lumbar range of motion (ROM), the EuroQol-5 Dimension (EQ-5D) health survey, the Health Utility Index III (HUI-III), and economic evaluation and safety data. Post-treatment follow-ups will be conducted at 1, 4, and 10 weeks after conclusion of treatment. This study will assess the comparative effectiveness of Chuna manual therapy compared to conventional usual care. Costs and effectiveness (utility) data will be analyzed for exploratory cost-effectiveness analysis. If this pilot study does not reach a definite conclusion due to its small sample size, these results will be used as preliminary results to calculate sample size for future large-scale clinical trials and contribute in the assessment of feasibility of a full-scale multicenter trial. Clinical Research Information Service (CRIS), KCT0001850 . Registered on 17 March 2016.

Twelve-Month Efficacy and Safety Data for the "Stress Incontinence Control, Efficacy and Safety Study": A Phase III, Multicenter, Prospective, Randomized, Controlled Study Treating Female Stress Urinary Incontinence Using the Vesair Intravesical Balloon.

PubMed

Winkler, Harvey; Jacoby, Karny; Kalota, Susan; Snyder, Jeffrey; Cline, Kevin; Robertson, Kaiser; Kahan, Randall; Green, Lonny; McCammon, Kurt; Rovner, Eric; Rardin, Charles

The "Stress Incontinence Control, Efficacy and Safety Study" (SUCCESS) is a phase III study of the Vesair Balloon in women with stress urinary incontinence who had failed conservative therapy, and either failed surgery, were not candidates for surgery, or chose not to have surgery. The safety and efficacy of the balloon at 12 months is reported for those participants in the treatment arm who elected to continue with the SUCCESS trial beyond the primary end point at 3 months. The SUCCESS trial is a multicenter, prospective, single-blinded, randomized, sham-controlled study. Participants were randomized on a 2.33:1 basis to either Vesair Balloon placement or placebo. The primary efficacy end point was a composite of both a greater than 50% reduction from baseline on 1-hour provocative pad weight test and an at least 10-point improvement in symptoms on the Incontinence Quality of Life questionnaire assessed at the 3-month study visit. Patients in the treatment arm who opted to continue in the trial were followed up prospectively up to 12 months. A total of 221 participants were randomized, including 157 in the treatment arm and 64 in the control arm. Sixty-seven participants in the treatment arm (42.7% of participants enrolled) were evaluated at 12 months, with 56.3% achieving the composite end point and 78.7% having greater than 50% reduction in pad weight from baseline in a per-protocol analysis. In an intent-to-treat analysis treating all participants who did not continue with the balloon as failures, 24% of the participants achieved the composite end point and 33.6% had a greater than 50% reduction in pad weight from baseline. Treatment-related adverse events in this group included dysuria (40.1%), gross hematuria (36.9%), and urinary tract infection (26.1%). In this phase III trial, symptom relief was maintained for those participants who continued therapy for 12 months. The balloon was found to be safe with no device- or procedure-related serious adverse events reported. Additional studies are warranted to determine which patient populations are more tolerant of the balloon and to assess the efficacy and safety of its longer-term use. Additional screening methods, including screening patients for balloon tolerability, are warranted to reduce participant withdrawals.

Impact of decision support in electronic medical records on lipid management in primary care.

PubMed

Gill, James M; Chen, Ying Xia; Glutting, Joseph J; Diamond, James J; Lieberman, Michael I

2009-10-01

Electronic decision-support tools may help to improve management of hyperlipidemia and other chronic diseases. This study examined the impact of lipid management tools integrated into an electronic medical record (EMR) in primary care practices. This randomized controlled trial was conducted in a national network of physicians who use an outpatient EMR. Adult primary care physicians were randomized by office to receive an electronic form that was embedded in the EMR. The form contained prompts regarding suboptimal care based on Adult Treatment Panel-III (ATP-III) guidelines, as well as reporting tools to identify patients outside of office visits whose lipid management was suboptimal. All active patients, ages 20-79 years, whose physicians participated in the study, were categorized as high, moderate, or low cardiovascular risk, and the proportion who were tested for hyperlipidemia, at lipid goal, and on lipid-lowering medications if not at goal were measured according to ATP-III guidelines. A total of 105 physicians from 25 offices and 64,150 patients were included in the study. Outcomes improved for most measures from before to 1 year after the intervention (November 1, 2005 to October 31, 2006). However, after controlling for confounding variables and for clustering in multilevel modeling, only up-to-date lipid testing for high-risk patients was statistically better in the intervention group as compared to the control group (adjusted odds ratio 15.0, P < 0.05). This study showed few differences in quality of lipid management after implementing an EMR-based disease management intervention in primary care settings. Future studies may need to examine more comprehensive interventions that include office staff in a team approach to care.

DRY CUPPING IN CHILDREN WITH FUNCTIONAL CONSTIPATION: A RANDOMIZED OPEN LABEL CLINICAL TRIAL.

PubMed

Shahamat, Mahmoud; Daneshfard, Babak; Najib, Khadijeh-Sadat; Dehghani, Seyed Mohsen; Tafazoli, Vahid; Kasalaei, Afshineh

2016-01-01

As a common disease in pediatrics, constipation poses a high burden to the community. In this study, we aimed to investigate the efficacy of dry cupping therapy (an Eastern traditional manipulative therapy) in children with functional constipation. One hundred and twenty children (4-18 years old) diagnosed as functional constipation according to ROME III criteria were assigned to receive a traditional dry cupping protocol on the abdominal wall for 8 minutes every other day or standard laxative therapy (Polyethylene glycol (PEG) 40% solution without electrolyte), 0.4 g/kg once daily) for 4 weeks, in an open label randomized controlled clinical trial using a parallel design with a 1:1 allocation ratio. Patients were evaluated prior to and following 2, 4, 8 and 12 weeks of the intervention commencement in terms of the ROME III criteria for functional constipation. There were no significant differences between the two arms regarding demographic and clinical basic characteristics. After two weeks of the intervention, there was a significant better result in most of the items of ROME III criteria of patients in PEG group. In contrast, after four weeks of the intervention, the result was significantly better in the cupping group. There was no significant difference in the number of patients with constipation after 4 and 8 weeks of the follow-up period. This study showed that dry cupping of the abdominal wall, as a traditional manipulative therapy, can be as effective as standard laxative therapy in children with functional constipation.

Effect of the 6-week home-based exercise program on physical activity level and physical fitness in colorectal cancer survivors: A randomized controlled pilot study.

PubMed

Lee, Mi Kyung; Kim, Nam Kyu; Jeon, Justin Y

2018-01-01

Despite improvement in prognosis of colorectal cancer, colorectal cancer survivors often suffer from adverse effects of cancer treatment, including reduced health-related fitness level. Therefore, this study aimed to examine the feasibility and efficacy of the 6-week home-based exercise program on the level of physical activity and physical fitness in stage II to III colorectal cancer survivors. Seventy-two stage II to III colorectal cancer survivors were randomly assigned to either a home-based exercise (n = 38) or usual care (n = 34) group for 6 weeks. The goal of the home-based exercise program was to increase the level of exercise to 18 metabolic equivalent task hours per week. The primary and the secondary outcomes of this study were physical activity level and physical fitness, respectively. A total of 57 participants (79.2%) completed the trial. Intention-to-treat analysis indicated that moderate physical activity level increased significantly by 269.4 ± 260.6 minutes per week in the exercise group (mean between-group difference, 254.6 minutes; 95% confidence interval, 172.7-434.7; p < 0.001). Physical fitness measured by using the step test (-3.9 vs. 2.6, p = 0.012) and push-up test (3.0 vs. -1.2, p = 0.012) also improved significantly in the exercise group compared to the control group. The 6-week home-based mixed aerobic and resistance exercise program was feasible and effective for increasing physical activity level and physical fitness in stage II to III colorectal cancer survivors.

Operator-Theoretic Modeling and Waveform Design for Radar in the Presence of Doppler

DTIC Science & Technology

2012-05-01

SPONSOR/MONITOR’S ACRONYM(S) ARO 8. PERFORMING ORGANIZATION REPORT NUMBER 19a. NAME OF RESPONSIBLE PERSON 19b. TELEPHONE NUMBER Alfred Hero III 734...Section III, is also underway. REFERENCES [1] R. J. Adler and J. E. Taylor, Random Fields and Geometry, Springer, 2006. [2] J. B. Conway, A Course in

Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette-Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study.

PubMed

Mordoh, José; Pampena, María Betina; Aris, Mariana; Blanco, Paula Alejandra; Lombardo, Mónica; von Euw, Erika María; Mac Keon, Soledad; Yépez Crow, Michelle; Bravo, Alicia Inés; O'Connor, Juan Manuel; Orlando, Ana Gabriela; Ramello, Franco; Levy, Estrella Mariel; Barrio, María Marcela

2017-01-01

The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is being tested against medium-dose IFN-α2b in stages IIB-III cutaneous melanoma (CM) patients (pts) after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663). Thirty-one pts were randomized to the CSF-470 vaccine ( n  = 20) or to the IFN-α2b arm ( n  = 11). During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 10 7 irradiated CSF-470 cells plus 10 6 colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2-4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU)/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL) were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS) for CSF-470 was observed ( p  = 0.022). Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1-2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs) were grade 1. Pts in the IFN-α2b arm presented grades 2-3 hematological (7/11), hepatic (2/11), and cardiac (1/11) toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm ( p  < 0.0001). Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.

Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

PubMed

Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Kim, Sang Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Lee, Kyung-Yil; Kim, Hwang Min; Choi, Young Youn; Ma, Sang Hyuk; Kim, Chun Soo; Kim, Dong Ho; Ahn, Dong Ho; Kang, Jin Han

2017-04-01

A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus. Copyright © 2015. Published by Elsevier B.V.

A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

PubMed Central

Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

2016-01-01

OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

A Phase III Randomized, Double-blind, Parallel-group Study to Evaluate the Efficacy and Safety of Acarmet (Metformin HCl 500 mg Plus Acarbose 50 mg Tablets) Versus Acarbose Alone in Subjects With Type 2 Diabetes Mellitus

ClinicalTrials.gov

2010-11-19

The Objectives of the Study is to Evaluate the Efficacy and Safety of Acarmet (Metformin HCl 500 mg; Plus Acarbose 50 mg Tablets) Thrice Daily Versus Acarbose 50 mg Thrice Daily Over 16 Weeks in; Subjects With Type 2 Diabetes Mellitus.

Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial.

PubMed

De Smedt, J; Van Kelst, S; Boecxstaens, V; Stas, M; Bogaerts, K; Vanderschueren, D; Aura, C; Vandenberghe, K; Lambrechts, D; Wolter, P; Bechter, O; Nikkels, A; Strobbe, T; Emri, G; Marasigan, V; Garmyn, M

2017-08-23

Previous studies have investigated the protective effect of vitamin D serum levels, at diagnosis and during the follow-up period after treatment, on melanoma outcome. In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor. This study is a multicenter randomized double blind placebo- controlled phase III trial. Patients between the age of 18 and 80 years diagnosed and treated surgically for a melanoma stage IB-III are eligible for randomization in a 1:1 ratio to active treatment or placebo. The study drug is taken each month and consists of either 100,000 International Unit cholecalciferol or arachidis oleum raffinatum used as a placebo. The primary endpoint is relapse free survival. The secondary endpoints are 25 hydroxyvitamin D3 serum levels at diagnosis and at 6 month intervals, melanoma subtype, melanoma site and stage of melanoma at diagnosis according to the 2009 American Joint Committee on Cancer melanoma staging and classification. At randomization a bloodsample is taken for DNA analysis. The study is approved by the local Ethics Committees. If we can confirm our hypothesis that vitamin D supplementation after removal of the tumor has a protective effect on relapse of cutaneous malignant melanoma we may reduce the burden of CMM at several levels. Patients, diagnosed with melanoma may have a better clinical outcome and improved quality of life. There will be a decrease in health care costs related to treatment of metastatic disease and there will be a decrease in loss of professional years, which will markedly reduce the economic burden of the disease. Clinical Trial.gov, NCT01748448 , 05/12/2012.

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

PubMed

Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

2016-03-15

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

A topological analysis of large-scale structure, studied using the CMASS sample of SDSS-III

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parihar, Prachi; Gott, J. Richard III; Vogeley, Michael S.

2014-12-01

We study the three-dimensional genus topology of large-scale structure using the northern region of the CMASS Data Release 10 (DR10) sample of the SDSS-III Baryon Oscillation Spectroscopic Survey. We select galaxies with redshift 0.452 < z < 0.625 and with a stellar mass M {sub stellar} > 10{sup 11.56} M {sub ☉}. We study the topology at two smoothing lengths: R {sub G} = 21 h {sup –1} Mpc and R {sub G} = 34 h {sup –1} Mpc. The genus topology studied at the R {sub G} = 21 h {sup –1} Mpc scale results in the highest genusmore » amplitude observed to date. The CMASS sample yields a genus curve that is characteristic of one produced by Gaussian random phase initial conditions. The data thus support the standard model of inflation where random quantum fluctuations in the early universe produced Gaussian random phase initial conditions. Modest deviations in the observed genus from random phase are as expected from shot noise effects and the nonlinear evolution of structure. We suggest the use of a fitting formula motivated by perturbation theory to characterize the shift and asymmetries in the observed genus curve with a single parameter. We construct 54 mock SDSS CMASS surveys along the past light cone from the Horizon Run 3 (HR3) N-body simulations, where gravitationally bound dark matter subhalos are identified as the sites of galaxy formation. We study the genus topology of the HR3 mock surveys with the same geometry and sampling density as the observational sample and find the observed genus topology to be consistent with ΛCDM as simulated by the HR3 mock samples. We conclude that the topology of the large-scale structure in the SDSS CMASS sample is consistent with cosmological models having primordial Gaussian density fluctuations growing in accordance with general relativity to form galaxies in massive dark matter halos.« less

Complementary and Alternative Approaches to Pain Relief During Labor

PubMed Central

Theau-Yonneau, Anne

2007-01-01

This review evaluated the effect of complementary and alternative medicine on pain during labor with conventional scientific methods using electronic data bases through 2006 were used. Only randomized controlled trials with outcome measures for labor pain were kept for the conclusions. Many studies did not meet the scientific inclusion criteria. According to the randomized control trials, we conclude that for the decrease of labor pain and/or reduction of the need for conventional analgesic methods: (i) There is an efficacy found for acupressure and sterile water blocks. (ii) Most results favored some efficacy for acupuncture and hydrotherapy. (iii) Studies for other complementary or alternative therapies for labor pain control have not shown their effectiveness. PMID:18227907

Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis.

PubMed

Mills, Edward; Wilson, Kumanan; Clarke, Mike; Foster, Brian; Walker, Scott; Rachlis, Beth; DeGroot, Nick; Montori, Victor M; Gold, Wayne; Phillips, Elizabeth; Myers, Stephen; Gallicano, Keith

2005-03-01

To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir. We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC(0-8)) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III). All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC(0-8) indinavir decreased by 4.4% (90% CI, -27.5% to -26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, -37.3% to +9%, P=0.25) in phase III. Control group mean AUC(0-8) decreased by 21.5% (90% CI, -43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, -55.3% to -15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle-indinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle-indinavir trials revealed a non-significant pooled mean difference of 1% in AUC(0-8) (95% CI, -53% to 55%, P=0.97). Indinavir levels were not reduced significantly in the presence of milk thistle.

Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

PubMed

Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

2015-01-01

A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.

Deinfibulation for preventing or treating complications in women living with type III female genital mutilation: A systematic review and meta-analysis.

PubMed

Okusanya, Babasola O; Oduwole, Olabisi; Nwachuku, Nuria; Meremikwu, Martin M

2017-02-01

Deinfibulation is a surgical procedure carried out to re-open the vaginal introitus of women living with type III female genital mutilation (FGM). To assess the impact of deinfibulation on gynecologic or obstetric outcomes by comparing women who were deinfibulated with women with type III FGM or women without FGM. Major databases including CENTRAL, MEDLINE, and Scopus were searched until August 2015. We included nonrandomized studies that compared obstetric outcomes of women with deinfibulation, type III FGM (not deinfibulated during labor), and no FGM. Quality of evidence was determined following the GRADE methodology. Summary measures were calculated using odds ratios at 95% confidence intervals. We found no randomized controlled trials. We included four case-control studies. The quality of evidence was very low. Compared with women with type III FGM at delivery, deinfibulated women had a significant reduction in the risk of having a cesarean delivery or postpartum hemorrhage. Compared with women without FGM, deinfibulated women had a similar risk of episiotomy, cesarean delivery, vaginal lacerations, postpartum hemorrhage, and blood loss at vaginal delivery. The length of second stage of labor, mean maternal hospital stay, and Apgar scores less than 7 were also comparable. Low-quality evidence suggests deinfibulation improves birth outcomes for women with type III FGM. CRD42015024466. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma.

PubMed

Kaufman, Howard L; Bines, Steven D

2010-06-01

There are few effective treatment options available for patients with advanced melanoma. An oncolytic herpes simplex virus type 1 encoding granulocyte macrophage colony-stimulating factor (GM-CSF; Oncovex(GM-CSF)) for direct injection into accessible melanoma lesions resulted in a 28% objective response rate in a Phase II clinical trial. Responding patients demonstrated regression of both injected and noninjected lesions highlighting the dual mechanism of action of Oncovex(GM-CSF) that includes both a direct oncolytic effect in injected tumors and a secondary immune-mediated anti-tumor effect on noninjected tumors. Based on these preliminary results a prospective, randomized Phase III clinical trial in patients with unresectable Stage IIIb or c and Stage IV melanoma has been initiated. The rationale, study design, end points and future development of the Oncovex(GM-CSF) Pivotal Trial in Melanoma (OPTIM) trial are discussed in this article.

Two Randomized Clinical Studies to Confirm Differential Plaque Removal by Sodium Bicarbonate Dentifrices in a Single Timed Brushing Model.

PubMed

Mason, Stephen; Karwal, Ritu; Bosma, Mary Lynn

2017-09-01

This study evaluated and compared plaque removal efficacy of commercially available dentifrices containing sodium bicarbonate (NaHCO3) to those without NaHCO3 in a single timed brushing clinical study model. Two randomized, examiner-blind, three-period, three-treatment, crossover studies were performed in adults with a mean Turesky modification of the Quigley-Hein Plaque Index (TPI) score of = 2.00. In Study 1, 60 subjects were randomized to commercially available dentifrices containing: (i) 67% NaHCO3 plus 1425 ppm fluoride (F) as sodium fluoride (NaF); (ii) 45% NaHCO3 plus 1425 ppm F as NaF; or (iii) 0% NaHCO3 plus silica and 1450 ppm F as NaF. In Study 2, 55 subjects were randomized to commercially available dentifrices containing: (i) 67% NaHCO3 plus 1425 ppm F as NaF; (ii) 0% NaHCO3 plus silica and 1400 ppm F as amine F/stannous F; or (iii) 0% NaHCO3 plus chlorhexidine/aluminum lactate and silica with 1360 ppm F as aluminum F. In both studies, subjects brushed their teeth for one timed minute under supervised conditions. Plaque was assessed pre- and post-brushing according to a six-site modification of the TPI. Mean TPI score was analyzed using an analysis of covariance model with treatment and study period as fixed effects, subject as a random variable, and pre-brushing score as a covariate. In both studies, mean TPI score decreased in all groups post-brushing compared with pre-brushing. In Study 1, statistically significant improvements in mean TPI score were reported with the 67% and 45% NaHCO3 dentifrices compared with the 0% NaHCO3 dentifrice (p = 0.0003 and p = 0.0005, respectively). In Study 2, improvements in mean TPI score were statistically significantly greater with the 67% NaHCO3 dentifrice compared with both 0% NaHCO3 dentifrices (p < 0.0001 for both comparisons). All dentifrices were generally well tolerated. A single timed brushing with commercially available dentifrices containing 67% or 45% NaHCO3 exerted a significantly greater effect on plaque removal than commercially available dentifrices without NaHCO3.

Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis.

PubMed

Ley, Brett; Swigris, Jeffrey; Day, Bann-Mo; Stauffer, John L; Raimundo, Karina; Chou, Willis; Collard, Harold R

2017-09-15

Respiratory-related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes. To compare the risk of nonelective hospitalization by type (all-cause, respiratory related, and non-respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials. Individual patient data was pooled from three phase III randomized, placebo-controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time-to-event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity. A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory-related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.77; P = 0.001), but all-cause (HR, 0.91; 95% CI, 0.70-1.19; P = 0.528) or non-respiratory-related hospitalization (HR, 1.32; 95% CI, 0.92-1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow-up. In a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory-related hospitalization over the course of 1 year. The effect of pirfenidone on death after hospitalization is uncertain.

Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial

PubMed Central

Yothers, Greg; O’Connell, Michael J.; Beart, Robert W.; Wozniak, Timothy F.; Pitot, Henry C.; Shields, Anthony F.; Landry, Jerome C.; Ryan, David P.; Arora, Amit; Evans, Lisa S.; Bahary, Nathan; Soori, Gamini; Eakle, Janice F.; Robertson, John M.; Moore, Dennis F.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Sharif, Saima; Roh, Mark S.; Wolmark, Norman

2015-01-01

Background: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. Methods: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. Results: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3–4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. Conclusions: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity. PMID:26374429

A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial.

PubMed

Man-Son-Hing, M; Laupacis, A; O'Connor, A M; Biggs, J; Drake, E; Yetisir, E; Hart, R G

1999-08-25

Decision aids are tools designed to help patients participate in the clinical decision-making process. To determine whether use of an audiobooklet (AB) decision aid explaining the results of a clinical trial affected the decision-making process of study participants. Randomized controlled trial conducted from May 1997 to April 1998. Fourteen centers that participated in the Stroke Prevention in Atrial Fibrillation (SPAF) III trial. A total of 287 patients from the SPAF III aspirin cohort study, in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years. At the end of SPAF III, participants were randomized to be informed of the study results with usual care plus use of an AB (AB group) vs usual care alone (control group). The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin. Patients' ability to make choices regarding antithrombotic therapy, and 6-month adherence to these decisions. Their knowledge, expectations, decisional conflict (the amount of uncertainty about the course of action to take), and satisfaction with the decision-making process were also measured. More patients in the AB group made a choice about antithrombotic therapy than in the control group (99% vs 94%; P = .02). Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage (in the AB group, 53%-80% correctly estimated different risks; in the control group, 16%-28% gave correct estimates). Decisional conflict and satisfaction were similar for the 2 groups. After 6 months, a similar percentage of patients were still taking their initial choice of antithrombotic therapy (95% vs 93%; P = .44). For patients with atrial fibrillation who had participated in a major clinical trial, the use of an AB decision aid improved their understanding of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take. Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical settings.

Acupressure in Controlling Nausea in Young Patients Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

Cancer.gov

RATIONALE: Acupressure wristbands may prevent or reduce nausea and caused by chemotherapy. It is not yet known whether standard care is more effective with or without acupressure wristbands in controlling acute and delayed nausea. PURPOSE: This randomized phase III trial is studying how well acupressure wristbands work with or without standard care in controlling nausea in

Camelina meal supplementation to beef cattle: III. Effects on acute-phase and thyroid responses

USDA-ARS?s Scientific Manuscript database

Sixty Angus x Hereford steers were ranked by BW on d -28 of the study and allocated to 20 drylot pens, which were randomly assigned to receive: 1) supplement containing (as-fed basis) 84% corn, 14% soybean meal, and 2% mineral mix (CO) offered during preconditioning (PC; d -28 to 0) and feedlot rece...

Comparison of Glucosamine-Chondroitin Sulfate with and without Methylsulfonylmethane in Grade I-II Knee Osteoarthritis: A Double Blind Randomized Controlled Trial.

PubMed

Lubis, Andri M T; Siagian, Carles; Wonggokusuma, Erick; Marsetyo, Aldo F; Setyohadi, Bambang

2017-04-01

Glucosamine, chondroitinsulfate are frequently used to prevent further joint degeneration in osteoarthritis (OA). Methylsulfonylmethane (MSM) is a supplement containing organic sulphur and also reported to slow anatomical joint progressivity in the knee OA. The MSM is often combined with glucosamine and chondroitin sulfate. However, there are controversies whether glucosamine-chondroitin sulfate or their combination with methylsulfonylmethane could effectively reduce pain in OA. This study is aimed to compare clinical outcome of glucosamine-chondroitin sulfate (GC), glucosamine-chondroitin sulfate-methylsulfonylmethane (GCM), and placeboin patients with knee osteoarthritis (OA) Kellgren-Lawrence grade I-II. a double blind, randomized controlled clinical trial was conducted on 147 patients with knee OA Kellgren-Lawrence grade I-II. Patients were allocated by permuted block randomization into three groups: GC (n=49), GCM (n=50), or placebo (n=48) groups. GC group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of saccharumlactis; GCM group received 1500 mg of glucosamine + 1200 mg of chondroitin sulfate + 500 mg of MSM; while placebo group received three matching capsules of saccharumlactis. The drugs were administered once daily for 3 consecutive months VAS and WOMAC scores were measured before treatment, then at 4th, 8th and 12th week after treatment. on statistical analysis it was found that at the 12th week, there are significant difference between three treatment groups on the WOMAC score (p=0.03) and on the VAS score (p=0.004). When analyzed between weeks, GCM treatment group was found statistically significant on WOMAC score (p=0.01) and VAS score (p<0.001). Comparing the score difference between weeks, WOMAC score analysis showed significant difference between GC, GCM, and placebo in week 4 (p=0.049) and week 12 (p=0.01). In addition, VAS score also showed significant difference between groups in week 8 (p=0.006) and week 12 (p<0.001). combination of glucosamine-chondroitinsulfate-methylsulfonylmethane showed clinical benefit for patients with knee OAK ellgren-Lawrence grade I-II compared with GC and placebo. GC did not make clinical improvement in overall groups of patients with knee OA Kellgren Lawrence grade I-II.

Randomized comparison of cost-saving and effectiveness of oral rapamycin plus bare-metal stents with drug-eluting stents: three-year outcome from the randomized oral rapamycin in Argentina (ORAR) III trial.

PubMed

Rodriguez, Alfredo E; Rodriguez-Granillo, Alfredo M; Antoniucci, David; Mieres, Juan; Fernandez-Pereira, Carlos; Rodriguez-Granillo, Gaston A; Santaera, Omar; Rubilar, Bibiana; Palacios, Igor F; Serruys, Patrick W

2012-09-01

The Oral Rapamycin in ARgentina (ORAR) III trial is a randomized study comparing a strategy of oral rapamycin (OR) plus bare-metal stent (BMS) versus a strategy of drug-eluting stents (DES) in patients with de novo coronary lesions. The purpose of this study was to assess the 3 years cost-effectiveness outcome of each strategy. OR after BMS has been associated with reduction of target vessel revascularization (TVR) although its value in long-term efficacy in comparison with DES is unknown. In three hospitals in Buenos Aires, Argentina, 200 patients were randomized to OR plus BMS (n = 100) or DES (n = 100). Primary objectives were costs and effectiveness. Cost analysis included in-hospital and follow-up costs. Safety was defined as the composite of death, myocardial infarction (MI), and stroke. Efficacy was defined as TVR. Baseline characteristics between groups were similar. The 3-year follow-up rate was 99%. Cardiac mortality was 2% and 5% in OR group and DES group, respectively (P = 0.44). The composite of death, MI and stroke rate was 11% in OR group and 20% in DES group (P = 0.078). TVR rate was 14.5% in OR group and 17.6% in DES group (P = 0.50), respectively. Three year cumulative costs were significantly lower in the OR arm as compared to the DES arm (P = 0.0001) and DES strategy did not result cost-effective according to the non-inferiority test. At 3 years follow-up, there were no differences in effectiveness between the two strategies, and DES strategy was not more cost-effective as compared to OR plus BMS. Copyright © 2011 Wiley Periodicals, Inc.

Efficacy and safety of bilastine in Japanese patients with chronic spontaneous urticaria: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II/III study.

PubMed

Hide, Michihiro; Yagami, Akiko; Togawa, Michinori; Saito, Akihiro; Furue, Masutaka

2017-04-01

Bilastine, a novel non-sedating second-generation H 1 -antihistamine, has been widely used in the treatment of allergic rhinoconjunctivitis and urticaria with a recommended dose of 20 mg once daily in most European countries since 2010. We evaluated its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU). We conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18-74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day -3 to 0) in total symptom score (TSS) at 2 weeks (Day 8-14), consisting of the itch and rash scores. A total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated. Two-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

A randomized controlled trial of intranasal ketamine in migraine with prolonged aura.

PubMed

Afridi, Shazia K; Giffin, Nicola J; Kaube, Holger; Goadsby, Peter J

2013-02-12

The aim of our study was to test the hypothesis that ketamine would affect aura in a randomized controlled double-blind trial, and thus to provide direct evidence for the role of glutamatergic transmission in human aura. We performed a double-blinded, randomized parallel-group controlled study investigating the effect of 25 mg intranasal ketamine on migraine with prolonged aura in 30 migraineurs using 2 mg intranasal midazolam as an active control. Each subject recorded data from 3 episodes of migraine. Eighteen subjects completed the study. Ketamine reduced the severity (p = 0.032) but not duration of aura in this group, whereas midazolam had no effect. These data provide translational evidence for the potential importance of glutamatergic mechanisms in migraine aura and offer a pharmacologic parallel between animal experimental work on cortical spreading depression and the clinical problem. This study provides class III evidence that intranasal ketamine is effective in reducing aura severity in patients with migraine with prolonged aura.

Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs.

PubMed

Valverde, Alexander; Cantwell, Shauna; Hernández, Jorge; Brotherson, Celeste

2004-01-01

To evaluate the anti-emetic properties of acepromazine in dogs receiving opioids as pre-anesthetic medication. Randomized prospective clinical study. One hundred and sixteen dogs (ASA I or II), admitted for elective surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 0.25-13.4 years of age, weighing 1.8-57.7 kg. A prospective clinical trial in which the dogs were randomly assigned to one of three groups. All groups received acepromazine (0.05 mg kg(-1) intramuscularly (i.m.)). Group I received acepromazine 15 minutes prior to opioid administration. Group II received acepromazine in combination with the opioid. Group III received acepromazine 15 minutes after opioid administration. One of three different opioids was administered i.m. to each dog: morphine sulfate at 0.5 mg kg(-1); hydromorphone hydrochloride at 0.1 mg kg(-1); or oxymorphone hydrochloride at 0.075 mg kg(-1). Dogs receiving acepromazine before the opioid (group I) had a significantly lower incidence of vomiting (18%) than dogs in groups II (45%) and III (55%). The degree of sedation was significantly lower in the dogs receiving the combination of acepromazine and the opioid (group II) than in dogs receiving the opioid as the first drug (group III). Acepromazine administered 15 minutes before the opioid lowers the incidence of vomiting induced by opioids.

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

PubMed

Papp, Kim A; Krueger, James G; Feldman, Steven R; Langley, Richard G; Thaci, Diamant; Torii, Hideshi; Tyring, Stephen; Wolk, Robert; Gardner, Annie; Mebus, Charles; Tan, Huaming; Luo, Yingchun; Gupta, Pankaj; Mallbris, Lotus; Tatulych, Svitlana

2016-05-01

Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. There was no dose comparison beyond week 52. Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

The role of platelet-rich plasma in arthroscopic rotator cuff repair: a systematic review with quantitative synthesis.

PubMed

Chahal, Jaskarndip; Van Thiel, Geoffrey S; Mall, Nathan; Heard, Wendell; Bach, Bernard R; Cole, Brian J; Nicholson, Gregory P; Verma, Nikhil N; Whelan, Daniel B; Romeo, Anthony A

2012-11-01

Despite the theoretic basis and interest in using platelet-rich plasma (PRP) to improve the potential for rotator cuff healing, there remains ongoing controversy regarding its clinical efficacy. The objective of this systematic review was to identify and summarize the available evidence to compare the efficacy of arthroscopic rotator cuff repair in patients with full-thickness rotator cuff tears who were concomitantly treated with PRP. We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PubMed for eligible studies. Two reviewers selected studies for inclusion, assessed methodologic quality, and extracted data. Pooled analyses were performed using a random effects model to arrive at summary estimates of treatment effect with associated 95% confidence intervals. Five studies (2 randomized and 3 nonrandomized with comparative control groups) met the inclusion criteria, with a total of 261 patients. Methodologic quality was uniformly sound as assessed by the Detsky scale and Newcastle-Ottawa Scale. Quantitative synthesis of all 5 studies showed that there was no statistically significant difference in the overall rate of rotator cuff retear between patients treated with PRP and those treated without PRP (risk ratio, 0.77; 95% confidence interval, 0.48 to 1.23). There were also no differences in the pooled Constant score; Simple Shoulder Test score; American Shoulder and Elbow Surgeons score; University of California, Los Angeles shoulder score; or Single Assessment Numeric Evaluation score. PRP does not have an effect on overall retear rates or shoulder-specific outcomes after arthroscopic rotator cuff repair. Additional well-designed randomized trials are needed to corroborate these findings. Level III, systematic review of Level I, II, and III studies. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Brief report: pulmonary auscultation in the operating room: a prospective randomized blinded trial comparing electronic and conventional stethoscopes.

PubMed

Hoffmann, Clement; Falzone, Elisabeth; Verret, Catherine; Pasquier, Pierre; Leclerc, Thomas; Donat, Nicolas; Jost, Daniel; Mérat, Stephane; Maurice, Guillaume de Saint; Lenoir, Bernard; Auroy, Yves; Tourtier, Jean-Pierre

2013-09-01

We compared the subjective quality of pulmonary auscultation between 2 acoustic stethoscopes (Holtex Ideal® and Littmann Cardiology III®) and an electronic stethoscope (Littmann 3200®) in the operating room. A prospective double-blind randomized study with an evaluation during mechanical ventilation was performed in 100 patients. After each examination, the listeners using a numeric scale (0-10) rated the quality of auscultation. Auscultation quality was compared in patients among stethoscopes with a multilevel mixed-effects linear regression with random intercept (operator effect), adjusted on significant factors in univariate analysis. A significant difference was defined as P < 0.05. One hundred comparative evaluations of pulmonary auscultation were performed. The quality of auscultation was rated 8.2 ± 1.6 for the electronic stethoscope, 7.4 ± 1.8 for the Littmann Cardiology III, and 4.6 ± 1.8 for the Holtex Ideal. Compared with Holtex Ideal, auscultation quality was significantly higher with other stethoscopes (P < 0.0001). Compared with Littmann Cardiology III, auscultation quality was significantly higher with Littmann 3200 electronic stethoscope (β = 0.9 [95% confidence interval, 0.5-1.3]). An electronic stethoscope can provide a better quality of pulmonary auscultation than acoustic stethoscopes in the operating room, yet with a magnitude of improvement marginally higher than that provided with a high performance acoustic stethoscope. Whether this can translate into a clinically relevant benefit requires further studies.

The relation between hypochondriasis and age.

PubMed

Barsky, A J; Frank, C B; Cleary, P D; Wyshak, G; Klerman, G L

1991-07-01

This study examined the relation between hypochondriasis and age while controlling for the possible confounding influences of medical morbidity, social isolation, and other psychiatric disorder. Consecutive patients attending a general medical clinic on randomly selected days were screened with a hypochondriasis self-report questionnaire. Those whose scores exceeded a preestablished cutoff level and a random sample of those who scored below it completed a research battery consisting of self-report questionnaires and structured interviews for DSM-III-R diagnoses of hypochondriasis and other axis I disorders. The patients' medical records were audited, and their physicians completed questionnaires about them. The 60 patients who met the DSM-III-R criteria for hypochondriasis at interview constituted the study group, and 100 patients randomly chosen from among those who scored below the cutoff for hypochondriasis constituted the comparison group. The hypochondriacal group was not older than the comparison group. Hypochondriacal patients aged 65 years and over did not differ significantly from younger hypochondriacal patients in hypochondriacal attitudes, somatization, tendency to amplify bodily sensation, or global assessment of their overall health, even though their aggregate medical morbidity was greater. The elderly hypochondriacal patients had higher levels of disability, but this appeared to be attributable to their medical status rather than to any increase in hypochondriasis. Within the comparison sample, subjects aged 65 years and over were not more hypochondriacal than those under 65 years of age. Hypochondriasis is found to some degree in all patients and appears to be unrelated to age.

A Randomized Controlled Trial Comparing Suture-Fixation Mucopexy and Doppler-Guided Hemorrhoidal Artery Ligation in Patients with Grade III Hemorrhoids

PubMed Central

Zhai, Min; Zhang, Yong-An; Wang, Zhen-Yi; Sun, Jian-Hua; Wen, Jie; Zhang, Qi; Li, Jin-De; Wu, Yi-Zheng; Zhou, Feng; Xu, Hui-Lei

2016-01-01

Background. We aimed to evaluate the effectiveness of a suture-fixation mucopexy procedure by comparing with Doppler-guided hemorrhoidal artery ligation (DGHAL) in the management of patients with grade III hemorrhoids. Methods. This was a randomized controlled trial. One hundred patients with grade III hemorrhoids were randomly assigned to receive suture-fixation mucopexy (n = 50) or DGHAL (n = 50). Outcome assessments were performed at 2 weeks, 12 months, and 24 months. Assessments included resolution of clinical symptoms, postoperative complications, duration of hospitalization, and total costs. Results. At 2 weeks, one (2%) patient in suture-fixation group and four (8%) patients in DGHAL group had persistent prolapsing hemorrhoids. Postoperative bleeding was observed in two patients (4%) in suture-fixation group and one patient in DGHAL group. There was no significant difference in short-term recurrence between groups. Postoperative complications and duration of hospitalization were comparable between the two groups. Rates of recurrence of prolapse or bleeding at 12 months did not differ between groups. However, recurrence of prolapse at 24 months was significantly more common in DGHAL group (19.0% versus 2.3%, p = 0.030). Conclusions. Compared with DGHAL, the suture-fixation mucopexy technique had comparable short-term outcomes and favorable long-term outcomes. PMID:27066071

The effects of biome and spatial scale on the Co-occurrence patterns of a group of Namibian beetles

NASA Astrophysics Data System (ADS)

Pitzalis, Monica; Montalto, Francesca; Amore, Valentina; Luiselli, Luca; Bologna, Marco A.

2017-08-01

Co-occurrence patterns (studied by C-score, number of checkerboard units, number of species combinations, and V-ratio, and by an empirical Bayes approach developed by Gotelli and Ulrich, 2010) are crucial elements in order to understand assembly rules in ecological communities at both local and spatial scales. In order to explore general assembly rules and the effects of biome and spatial scale on such rules, here we studied a group of beetles (Coleoptera, Meloidae), using Namibia as a case of study. Data were gathered from 186 sampling sites, which allowed collection of 74 different species. We analyzed data at the level of (i) all sampled sites, (ii) all sites stratified by biome (Savannah, Succulent Karoo, Nama Karoo, Desert), and (iii) three randomly selected nested areas with three spatial scales each. Three competing algorithms were used for all analyses: (i) Fixed-Equiprobable, (ii) Fixed-Fixed, and (iii) Fixed-Proportional. In most of the null models we created, co-occurrence indicators revealed a non-random structure in meloid beetle assemblages at the global scale and at the scale of biomes, with species aggregation being much more important than species segregation in determining this non-randomness. At the level of biome, the same non-random organization was uncovered in assemblages from Savannah (where the aggregation pattern was particularly strong) and Succulent Karoo, but not in Desert and Nama Karoo. We conclude that species facilitation and similar niche in endemic species pairs may be particularly important as community drivers in our case of study. This pattern is also consistent with the evidence of a higher species diversity (normalized according to biome surface area) in the two former biomes. Historical patterns were perhaps also important for Succulent Karoo assemblages. Spatial scale had a reduced effect on patterning our data. This is consistent with the general homogeneity of environmental conditions over wide areas in Namibia.

A systematic review and mixed treatment comparison of monotherapy in early Parkinson's disease: implications for Latin America.

PubMed

Márquez-Cruz, Maribel; Díaz-Martínez, Juan Pablo; Soto-Molina, Herman; De Saráchaga, Adib Jorge; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Rodríguez-Violante, Mayela

2016-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. There are no clinical trials comparing all available pharmacological therapies for the treatment of early PD. The objective of this review is to indirectly analyze the efficacy of antiparkinson drugs currently available in Latin America. A systematic review was performed exploring only placebo-controlled randomized trials comparing antiparkinson monotherapy (levodopa, pramipexole, rasagiline, or selegiline) in patients with PD on Hoehn and Yahr stages I through III published from January 1994 to May 2014. The primary outcome was the mean change in the Unified PD Rating Scale (UPDRS) I, II and III. A mixed treatment comparison analysis (indirect comparisons) through a random-effects model was performed. Levodopa demonstrated the highest effects in terms of UPDRS score improvement both from baseline and when compared to other treatments. Levodopa showed a 60.1% probability of granting the greatest reduction in UPDRS I, II and III.

A Study of Parental Attitudes and Values Towards Education on the Navajo and Hopi Reservations. Part III, Parental Values.

ERIC Educational Resources Information Center

Biglin, J. E.; And Others

In order to determine what the parents of children attending public school on the Navajo and Hopi reservations want of education, a random sample of 10% of all parents having 1 or more children in attendance in 1 of the 6 public school districts on the reservations was taken. For the segment of the study described in this volume, a projective-type…

Efficacy and safety of tofacitinib for active rheumatoid arthritis with an inadequate response to methotrexate or disease-modifying antirheumatic drugs: a meta-analysis of randomized controlled trials

PubMed Central

Song, Gwan Gyu; Bae, Sang-Cheol

2014-01-01

Background/Aims The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA). Methods A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches. Results Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. Conclusions Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile. PMID:25228842

German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer.

PubMed

von Minckwitz, Gunter; Möbus, Volker; Schneeweiss, Andreas; Huober, Jens; Thomssen, Christoph; Untch, Michael; Jackisch, Christian; Diel, Ingo J; Elling, Dirk; Conrad, Bettina; Kreienberg, Rolf; Müller, Volkmar; Lück, Hans-Joachim; Bauerfeind, Ingo; Clemens, Michael; Schmidt, Marcus; Noeding, Stefanie; Forstbauer, Helmut; Barinoff, Jana; Belau, Antje; Nekljudova, Valentina; Harbeck, Nadia; Loibl, Sibylle

2013-10-01

Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use. The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed. Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093). Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.

Chronic use of PAH-specific therapy in World Health Organization Group III Pulmonary Hypertension: a systematic review and meta-analysis.

PubMed

Prins, Kurt W; Duval, Sue; Markowitz, Jeremy; Pritzker, Marc; Thenappan, Thenappan

2017-03-01

Pulmonary hypertension (PH) complicating chronic obstructive pulmonary disease (COPD-PH) and interstitial lung disease (ILD-PH) (World Health Organization [WHO] Group III PH) increases medical costs and reduces survival. Despite limited data, many clinicians are using pulmonary arterial hypertension (PAH)-specific therapy to treat WHO Group III PH patients. To further investigate the utility of PAH-specific therapy in WHO Group III PH, we performed a systematic review and meta-analysis. Relevant studies from January 2000 through May 2016 were identified in the MEDLINE, EMBASE, and COCHRANE electronic databases and www.clinicaltrials.gov. Change in six-minute walk distance (6MWD) was estimated using random effects meta-analysis techniques. Five randomized controlled trials (RCTs) in COPD-PH (128 placebo or standard treatment and 129 PAH-medication treated patients), two RCTs in ILD-PH (23 placebo and 46 treated patients), and four single-arm clinical trials (50 patients) in ILD-PH were identified. Treatment in both COPD-PH and ILD-PH did not worsen hypoxemia. Symptomatic burden was not consistently reduced but there were trends for reduced pulmonary artery pressures and pulmonary vascular resistance with PAH-specific therapy. As compared to placebo, 6MWD was not significantly improved with PAH-specific therapy in the five COPD-PH RCTs (42.7 m; 95% confidence interval [CI], -1.0 - 86.3). In the four single-arm studies in ILD-PH patients, there was a significant improvement in 6MWD after PAH-specific treatment (46.2 m; 95% CI, 27.9-64.4), but in the two ILD-PH RCTs there was not an improvement (21.6 m; 95% CI, -17.8 - 61.0) in exercise capacity when compared to placebo. Due to the small numbers of patients evaluated and inconsistent beneficial effects, the utility of PAH-specific therapy in WHO Group III PH remains unproven. A future clinical trial that is appropriately powered is needed to definitively determine the efficacy of this widely implemented treatment approach.

s-core network decomposition: A generalization of k-core analysis to weighted networks

NASA Astrophysics Data System (ADS)

Eidsaa, Marius; Almaas, Eivind

2013-12-01

A broad range of systems spanning biology, technology, and social phenomena may be represented and analyzed as complex networks. Recent studies of such networks using k-core decomposition have uncovered groups of nodes that play important roles. Here, we present s-core analysis, a generalization of k-core (or k-shell) analysis to complex networks where the links have different strengths or weights. We demonstrate the s-core decomposition approach on two random networks (ER and configuration model with scale-free degree distribution) where the link weights are (i) random, (ii) correlated, and (iii) anticorrelated with the node degrees. Finally, we apply the s-core decomposition approach to the protein-interaction network of the yeast Saccharomyces cerevisiae in the context of two gene-expression experiments: oxidative stress in response to cumene hydroperoxide (CHP), and fermentation stress response (FSR). We find that the innermost s-cores are (i) different from innermost k-cores, (ii) different for the two stress conditions CHP and FSR, and (iii) enriched with proteins whose biological functions give insight into how yeast manages these specific stresses.

Prevention of Posttraumatic Contractures with Ketotifen (PERK)

DTIC Science & Technology

2017-10-01

opportunity to design a Phase III RCT on the use of ketotifen in post -traumatic joint contractures. The goal is to design and develop the infrastructure to...Research (CIHR) for the Phase III RCT. 2. KEYWORDS Post -traumatic contractures, elbow fractures, randomized clinical trial, multicenter, ketotifen...application to use ketotifen in post -traumatic joint contracture prevention was submitted to the Division of Pulmonary, Allergy, and Rheumatology

Land Plus Aquatic Therapy Versus Land-Based Rehabilitation Alone for the Treatment of Balance Dysfunction in Parkinson Disease: A Randomized Controlled Study With 6-Month Follow-Up.

PubMed

Palamara, Grazia; Gotti, Francesco; Maestri, Roberto; Bera, Rossana; Gargantini, Roberto; Bossio, Fabiola; Zivi, Ilaria; Volpe, Daniele; Ferrazzoli, Davide; Frazzitta, Giuseppe

2017-06-01

To assess whether a specific land-based physical intervention with the inclusion of aquatic therapy is more effective than land-based rehabilitation alone for the treatment of balance dysfunction in patients with Parkinson disease (PD), immediately after therapy and at 6 months' follow-up. Randomized controlled study with 6-month follow-up. A PD and brain injury rehabilitation department in a general hospital. Patients (N=34) with moderate-stage PD. Seventeen patients underwent a land-based rehabilitation protocol called multidisciplinary intensive rehabilitation treatment (MIRT), and 17 underwent MIRT plus aquatic therapy (MIRT-AT). The primary outcome measure was the Berg Balance Scale (BBS); secondary outcome measures were the Unified Parkinson Disease Rating Scale parts II and III (UPDRS II/III) and the Timed Up and Go (TUG) test. These measures were assessed in both groups at admission, at discharge, and after 6 months. BBS improved after treatment in both groups. Even though no statistically significant difference between groups was observed at each observation time, BBS scores at follow-up were significantly higher than at baseline in MIRT-AT patients. Both groups also showed an improvement in UPDRS II/III and TUG at the end of treatment compared with baseline, but these findings were lost at the 6-month follow-up. Aquatic therapy added to land-based rehabilitation could provide a contribution to the treatment of balance dysfunction in patients with moderate-stage PD. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

DRY CUPPING IN CHILDREN WITH FUNCTIONAL CONSTIPATION: A RANDOMIZED OPEN LABEL CLINICAL TRIAL

PubMed Central

Shahamat, Mahmoud; Daneshfard, Babak; Najib, Khadijeh-Sadat; Dehghani, Seyed Mohsen; Tafazoli, Vahid; Kasalaei, Afshineh

2016-01-01

Background: As a common disease in pediatrics, constipation poses a high burden to the community. In this study, we aimed to investigate the efficacy of dry cupping therapy (an Eastern traditional manipulative therapy) in children with functional constipation. Materials and Methods: One hundred and twenty children (4-18 years old) diagnosed as functional constipation according to ROME III criteria were assigned to receive a traditional dry cupping protocol on the abdominal wall for 8 minutes every other day or standard laxative therapy (Polyethylene glycol (PEG) 40% solution without electrolyte), 0.4 g/kg once daily) for 4 weeks, in an open label randomized controlled clinical trial using a parallel design with a 1:1 allocation ratio. Patients were evaluated prior to and following 2, 4, 8 and 12 weeks of the intervention commencement in terms of the ROME III criteria for functional constipation. Results: There were no significant differences between the two arms regarding demographic and clinical basic characteristics. After two weeks of the intervention, there was a significant better result in most of the items of ROME III criteria of patients in PEG group. In contrast, after four weeks of the intervention, the result was significantly better in the cupping group. There was no significant difference in the number of patients with constipation after 4 and 8 weeks of the follow-up period. Conclusion: This study showed that dry cupping of the abdominal wall, as a traditional manipulative therapy, can be as effective as standard laxative therapy in children with functional constipation. PMID:28852716

Comparison of the Tight Rope Technique and Clavicular Hook Plate for the Treatment of Rockwood Type III Acromioclavicular Joint Dislocation.

PubMed

Cai, Leyi; Wang, Te; Lu, Di; Hu, Wei; Hong, Jianjun; Chen, Hua

2018-06-01

Acromioclavicular joint dislocation is one of the most common shoulder problems and may lead to instability or degenerative changes. The aim of this study was to compare the clinical outcomes of the Tight Rope system and clavicular hook plate for Rockwood type III acromioclavicular joint dislocation in adults. This was a prospective, randomized study in a hospital setting. From January 2012 to December 2014, 69 patients with type III injury were reviewed. Patients were randomly divided into two groups: Group A was treated using the TightRope system and Group B with the clavicular hook plate. All participants were followed up for 12 months. Clinical outcomes, radiological results and postoperative complications were recorded. The length of incision was significantly shorter in Goup A than that in Group B. The blood loss of surgery was significantly less in the Group A. Significant difference could be found between the two groups regarding the Visual Analogue Scale scores one day after surgery, at the 3 and 12 months follow-up. There were no differences according to the improvement of the Constant-Murley score and the coracoclavicular distance between the groups. The two groups have similar clinical and radiological outcomes. Both treatments could relieve the pain of dislocation, improve the function of Acromioclavicular joint and rectify the coracoclavicular distance measured in plain films. However, the TightRope system exhibited some advantages in terms of length of incision, blood loss of surgery, the pain postoperatively and no need for a second surgery.

A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of β-D-mannuronic acid in rheumatoid arthritis patients.

PubMed

Ahmadi, Hossein; Jamshidi, Ahmad Reza; Gharibdoost, Farhad; Mahmoudi, Mahdi; Rastkari, Noushin; Mostafaei, Shayan; Fattahi, Mohammad Javad; Vojdanian, Mahdi; Cuzzocrea, Salvatore; Rehm, Bernd H A; Matsuo, Hidenori; Hosseini, Mostafa; Aghazadeh, Zahra; Mortazavi-Jahromi, Seyed Shahabeddin; Mirshafiey, Abbas

2018-06-01

Following the potent efficacy of β-D-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy. The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety. There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient's adverse events occurred during this study. Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.

Reduced-Intensity Delayed Intensification in Standard-Risk Pediatric Acute Lymphoblastic Leukemia Defined by Undetectable Minimal Residual Disease: Results of an International Randomized Trial (AIEOP-BFM ALL 2000).

PubMed

Schrappe, Martin; Bleckmann, Kirsten; Zimmermann, Martin; Biondi, Andrea; Möricke, Anja; Locatelli, Franco; Cario, Gunnar; Rizzari, Carmelo; Attarbaschi, Andishe; Valsecchi, Maria Grazia; Bartram, Claus R; Barisone, Elena; Niggli, Felix; Niemeyer, Charlotte; Testi, Anna Maria; Mann, Georg; Ziino, Ottavio; Schäfer, Beat; Panzer-Grümayer, Renate; Beier, Rita; Parasole, Rosanna; Göhring, Gudrun; Ludwig, Wolf-Dieter; Casale, Fiorina; Schlegel, Paul-Gerhardt; Basso, Giuseppe; Conter, Valentino

2018-01-20

Purpose Delayed intensification (DI) is an integral part of treatment of childhood acute lymphoblastic leukemia (ALL), but it is associated with relevant toxicity. Therefore, standard-risk patients of trial AIEOP-BFM ALL 2000 (Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With ALL) were investigated with the specific aim to reduce treatment intensity. Patients and Methods Between July 2000 and July 2006, 1,164 patients (1 to 17 years of age) with standard-risk ALL (defined as the absence of high-risk cytogenetics and undetectable minimal residual disease on days 33 and 78) were randomly assigned to either experimental reduced-intensity DI (protocol III; P-III) or standard DI (protocol II; P-II). Cumulative drug doses of P-III were reduced by 30% for dexamethasone and 50% for vincristine, doxorubicin, and cyclophosphamide, which shortened the treatment duration from 49 to 29 days. The study aimed at noninferiority of reduced-intensity P-III; analyses were performed according to treatment given. Results For P-III and P-II, respectively, the 8-year rate of disease-free survival (± SE) was 89.2 ± 1.3% and 92.3 ± 1.2% ( P = .04); cumulative incidence of relapse, 8.7 ± 1.2% and 6.4 ± 1.1% ( P = .09); and overall survival, 96.1 ± 0.8% and 98.0 ± 0.6% ( P = .06). Patients with ETV6-RUNX1-positive ALL and patients 1 to 6 years of age performed equally well in both arms. The incidence of death during remission was comparable, which indicates equivalent toxicity. The 8-year cumulative incidence rate of secondary malignancies was 1.3 ± 0.5% and 0.6 ± 0.4% for P-III and P-II, respectively ( P = .37). Conclusion Although the criteria used for the standard-risk definition in this trial identified patients with exceptionally good prognosis, reduction of chemotherapy was not successful mainly because of an increased rate of relapse. The data suggest that treatment reduction is feasible in specific subgroups, which underlines the biologic heterogeneity of this cohort selected according to treatment response.

Chemoradiotherapy With or Without AE-941 in Stage III Non–Small Cell Lung Cancer: A Randomized Phase III Trial

PubMed Central

Lee, J. Jack; Komaki, Ritsuko; Herbst, Roy S.; Feng, Lei; Evans, William K.; Choy, Hak; Desjardins, Pierre; Esparaz, Benjamin T.; Truong, Mylene T.; Saxman, Scott; Kelaghan, Joseph; Bleyer, Archie; Fisch, Michael J.

2010-01-01

Background AE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non–small cell lung cancer (NSCLC). Methods A randomized, double-blinded, placebo-controlled, phase III clinical trial was designed to test the efficacy of AE-941 in unresectable stage III NSCLC patients who were treated with chemoradiotherapy. Between June 5, 2000, and February 6, 2006, 379 eligible patients were enrolled in community and academic oncology centers across the United States and Canada. In February 2006, the trial was closed to new patient entry before meeting the target sample size because of insufficient accrual. All subjects received induction chemotherapy followed by concurrent chemotherapy with chest radiotherapy. Each participating center administered one of the two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. The primary endpoint was overall survival, and secondary endpoints were time to progression, progression-free survival, tumor response rate, and toxic effects. Event–time distributions were estimated by the Kaplan–Meier method. All statistical tests were two-sided. Results There was no statistically significant difference in overall survival between the chemoradiotherapy plus AE-941 group (n = 188; median survival = 14.4 months, 95% confidence interval = 12.6 to 17.9 months) and the chemoradiotherapy plus placebo group (n = 191; median survival = 15.6 months, 95% confidence interval = 13.8 to 18.1 months) (P = .73). Time to progression, progression-free survival, and tumor response rates were not statistically significantly different between the AE-941 and the placebo groups. No differences between the two groups were observed in common grade 3 or higher toxic effects attributable to chemoradiotherapy. Conclusions The addition of AE-941 to chemoradiotherapy did not improve overall survival in patients with unresectable stage III NSCLC. This study does not support the use of shark cartilage–derived products as therapy for lung cancer. PMID:20505152

Cost-effectiveness of New Surgical Treatments for Hemorrhoidal Disease: A Multicentre Randomized Controlled Trial Comparing Transanal Doppler-guided Hemorrhoidal Artery Ligation With Mucopexy and Circular Stapled Hemorrhoidopexy.

PubMed

Lehur, Paul A; Didnée, Anne S; Faucheron, Jean-Luc; Meurette, Guillaume; Zerbib, Philippe; Siproudhis, Laurent; Vinson-Bonnet, Béatrice; Dubois, Anne; Casa, Christine; Hardouin, Jean-Benoit; Durand-Zaleski, Isabelle

2016-11-01

To compare Doppler-guided hemorrhoidal artery ligation (DGHAL) with circular stapled hemorrhoidopexy (SH) in the treatment of grade II/III hemorrhoidal disease (HD). DGHAL is a treatment option for symptomatic HD; existing studies report limited risk and satisfactory outcomes. DGHAL has never before been compared with SH in a large-scale multi-institutional randomized clinical trial. Three hundred ninety-three grade II/III HD patients recruited in 22 centers from 2010 to 2013 were randomized to DGHAL (n = 197) or SH (n = 196). The primary endpoint was operative-related morbidity at 3 months (D.90) based on the Clavien-Dindo surgical complications grading. Total cost, cost-effectiveness, and clinical outcome were assessed at 1 year. At D.90, operative-related adverse events occurred after DGHAL and SH, respectively, in 47 (24%) and 50 (26%) patients (P = 0.70). DGHAL resulted in longer mean operating time (44±16 vs 30±14 min; P < 0.001), less pain (postoperative and at 2 wks visual analogic scale: 2.2 vs 2.8; 1.3 vs 1.9; P = 0.03; P = 0.013) and shorter sick leave (12.3 vs 14.8 d; P = 0.045). At 1 year, DGHAL led to more residual grade III HD (15% vs 5%) and a higher reoperation rate (8% vs 4%). Patient satisfaction was >90% for both procedures. Total cost at 1 year was greater for DGHAL [&OV0556;2806 (&OV0556;2670; 2967) vs &OV0556;2538 (&OV0556;2386; 2737)]. The D.90, incremental cost-effectiveness ratio (ICER) was &OV0556;7192 per averted complication. At 1 year DGHAL strategy was dominated. DGHAL and SH are viable options in grade II/III HD with no significant difference in operative-related risk. Although resulting in less postoperative pain and shorter sick leave, DGHAL was more expensive, took longer, and provided a possible inferior anatomical correction suggesting an increased risk of recurrence.

Modified radial v/s biatrial maze for atrial fibrillation in rheumatic valvular heart surgery.

PubMed

Sayed, Sajid A; Katewa, Ashish; Srivastava, Vivek; Jana, Sujit; Patwardhan, Anil M

2014-01-01

Atrial fibrillation (AF) is commonest sustained atrial arrhythmia producing high morbidity. Although Cox's Maze III procedure cures AF in majority, reduced atrial transport function (ATF) is a concern. Radial approach with ablation lines radial from sinus node towards atrioventricular annulii and parallel to atrial coronary arteries, has shown better ATF. Single blind open randomized prospective study of 80 patients was undertaken in two groups (40 each) of modified Cox's maze III and modified radial approach, to evaluate conversion to normal sinus rhythm (NSR) and ATF. Patients undergoing surgery for rheumatic valvular heart disease with continuous AF were prospectively randomized. Ablation lines were created with radiofrequency (RF) bipolar coagulation with cryoablation for the isthmal lesions and coronary sinus. Results were compared at 6 months and ATF was evaluated by atrial filling fraction (AFF) and A/E ratio on echocardiography. The rate of conversion to NSR in both groups was statistically insignificant by Fisher's exact test (p > 0.05). ATF was better in modified radial approach compared to modified Cox's Maze III (A/E compared by unpaired t test:0.52 ± 0.08 v/s 0.36 ± 0.10; p < 0.05. AFF compared using Mann Whitney U test: median AFF for radial group was 23 v/s 20 for biatrial group; p < 0.05). In patients with AF undergoing rheumatic valvular surgery, radiofrequency radial approach is as effective as modified Cox's maze III for conversion to NSR with better atrial transport function. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

[Prospective randomized study of HMVP, MVP, and HVP regimens in treatment of advanced non-small cell lung cancer].

PubMed

Gao, Jian-Fei; Li, Chang-Sheng; Zhang, Bi-Cheng; Du, Guang-Zu; Zhang, Xin-Hua; Wang, Jun; Zhu, Yu-Ze; Ou, Wu-Ling; Yang, Bo

2004-04-01

Non-small cell lung cancer (NSCLC) is hyposensitive to the normal first and second-line chemotherapy regimens. Camptothecin derivative is becoming a hot point in the treatment of advanced NSCLC. The objective of this article was to evaluate the response, toxicity, and survival time of HMVP, MVP, and HVP regimens (detail in below) in the treatment of advanced NSCLC. A total of 134 cases with advanced NSCLC was randomized into three groups: HMVP group [46 patients, hydroxycamptothecin (HCPT) 12 mg/m(2) from d1 to d5, mitomycin C (MMC) 6 mg/m(2) d1, vindesine (VDS) 2.5-3 mg/m(2) d1 and d8, cisplatin (DDP) 50 mg/m(2) d2 and d3], MVP group (44 patients, MMC, VDS and DDP were the same as HMVP group) and HVP group (44 patients, HCPT, VDS, DDP were the same as HMVP group). The response rates were 39.54% (17/43), 35.57% (15/42), and 26.19% (11/42) in HMVP, MVP, and HVP groups, respectively; no significant difference was detected among the three groups (P >0.05). No significant difference was detected in the median time of remission, median survival time, and 1-, 2-year survival rates among the three groups. Moreover, no significant difference was detected in grade III-IV leukopenia, grade III-IV thrombocytopenia, grade III-IV nausea and vomiting and grade III-IV constipation among the three groups. The response rate of MVP regimen is slightly lower than that of HMVP regimen, but HMVP regimen do not show obvious superiority. It may increase toxicities such as leukopenia, nausea/vomiting, and constipation. The response rate of HVP regimen is slightly lower than that of MVP regimen.

Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

Cancer.gov

This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve

Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

Cancer.gov

This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may

Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

PubMed Central

Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

2014-01-01

Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

Study protocol on comparative effectiveness of mindfulness meditation and qigong on psychophysiological outcomes for patients with colorectal cancer: a randomized controlled trial.

PubMed

Ho, Rainbow T H; Wan, Adrian H Y; Chan, Jessie S M; Ng, S M; Chung, K F; Chan, Cecilia L W

2017-08-08

Colorectal cancer imposes threats to patients' well-being. Although most physical symptoms can be managed by medication, psychosocial stressors may complicate survival and hamper quality of life. Mindfulness and Qigong, two kinds of mind-body exercise rooted in Eastern health philosophy, has been found effective in symptoms management, improving mental health, and reducing stress. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the comparative effectiveness of mindfulness and Baduanjin intervention on the bio-psychosocial wellbeing of people with colorectal cancer. A 3-arm RCT with waitlist control design will be used in this study. One hundred eighty-nine participants will be randomized into (i) Mindfulness, (ii) Baduanjin, or (iii) waitlist control groups. Participants in both the Baduanjin and mindfulness groups will receive 8-weeks of specific intervention. All three groups will undergo four assessment phases: (i) at baseline, (ii) at 4-week, (iii) at 8-week (post-intervention), and 6-month post-intervention (maintenance). All participants will be assessed in terms of cancer-related symptoms and symptom distress, mental health status, quality of life, stress level based on physiological marker. Based on prior research studies, participants in both the mindfulness and Baduanjn intervention group are expected to have better symptoms management, lower stress level, better mental health, and higher level of quality of life than the control group. This study contributes to better understanding on the common and unique effectiveness of mindfulness and Baduanjin qigong, as such patients and qualified healthcare professionals can select or provide practices which will produce maximum benefits, satisfaction, adherence, and sustainability. The trial has been registered in the Clinical Trials Centre of the University of Hong Kong ( HKCTR-2198 ) on 08 March 2017.

Randomized phase II study of sequential carboplatin plus paclitaxel and gefitinib in chemotherapy-naïve patients with advanced or metastatic non-small-cell lung cancer: Long-term follow-up results.

PubMed

Kubo, Emi; Yamamoto, Noboru; Nokihara, Hiroshi; Fujiwara, Yutaka; Horinouchi, Hidehito; Kanda, Shintaro; Goto, Yasushi; Ohe, Yuichiro

2017-01-01

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib was initially approved in Japan in 2002 for the treatment of advanced or metastatic non-small-cell lung cancer (NSCLC); however, the optimal order of conventional cytotoxic chemotherapy (carboplatin and paclitaxel) and gefitinib administration has not been determined. We conducted a randomized phase II study of carboplatin and paclitaxel followed by gefitinib vs. gefitinib followed by carboplatin and paclitaxel to select a candidate for further development in a phase III study of chemotherapy-naïve patients with advanced or metastatic NSCLC, regardless of their EGFR mutation status. A total of 97 patients meeting this description were randomly assigned to arm A (carboplatin and paclitaxel followed by gefitinib; n=49) or B (gefitinib followed by carboplatin and paclitaxel; n=48) from June, 2003 to October, 2005. Carboplatin and paclitaxel were administered in 4 cycles every 3 weeks; gefitinib was continued until disease progression or development of unacceptable toxicity. The primary endpoint was overall survival; the secondary endpoints were response rate and adverse event prevalence. The median overall follow-up was 65.1 months (range, 28.7-75.1 months). The major toxicities were hematological (carboplatin and paclitaxel) or skin rash, diarrhea and hepatic dysfunction (gefitinib). Interstitial lung disease was observed in 1 patient from each arm. In arms A and B, the carboplatin and paclitaxel response rate, gefitinib response rate, and median survival durations were 34.8 and 26.5%, 33.3 and 35.7%, and 18.8 and 17.2 months, respectively. Arm A was selected for a subsequent phase III study.

A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nonsmall cell lung cancer.

PubMed

Yuan, Shuanghu; Sun, Xindong; Li, Minghuan; Yu, Jinming; Ren, Ruimei; Yu, Yonghu; Li, Jianbin; Liu, Xiuqing; Wang, Renben; Li, Baosheng; Kong, Li; Yin, Yong

2007-06-01

Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field irradiation (IFI) in patients with nonsmall cell lung cancer (NSCLC). A total of 200 eligible patients with inoperable stage III NSCLC were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. A total of 4 to 6 cycles of cisplatin-based chemotherapy were delivered, and concurrent radiotherapy was started after the second cycle of chemotherapy. Three-dimensional conformal radiotherapy was delivered in once-daily fractions of 1.8 to 2 Gy to 68 to 74 Gy for IFI or 60 to 64 Gy for ENI. Patients in the IFI arm achieved better overall response rate (90% vs. 79%, P = 0.032) and better 5-years local control rate (51% vs.36%, P = 0.032) than those in the ENI arm. The radiation pneumonitis rate in patients with IFI was lower than in patients with ENI (17% vs. 29%, P = 0.044), and similar trends appeared in the radiation esophagitis, myelosuppression, and radiation pericarditis between 2 study arms, although not significantly. The 1-, 2-, and 5-year survival rates were 60.4%, 25.6%, and 18.3% for the ENI arm and 69.9%, 39.4%, and 25.1% for the IFI arm, respectively. Only the 2-year survival rates were statistically significant (P = 0.048). IFI arm achieved better overall response and local control than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to patients with inoperable stage III NSCLC. Outcome improvement can be expected by conformal IFI combined with chemotherapy for stage III NSCLC.

Forecasting patient outcomes in the management of hyperlipidemia.

PubMed

Brier, K L; Tornow, J J; Ries, A J; Weber, M P; Downs, J R

1999-03-22

To forecast adult patient outcomes in the management of hyperlipidemia using adult National Health and Examination Survey III (NHANES III) population statistics and National Cholesterol Education Program (NCEP) guidelines for goals of therapy. Review of the hyperlipidemia drug therapy English-language medical literature with emphasis on randomized controlled trials of more than 6 weeks' duration published in the last 7 years, product package inserts, US Food and Drug Administration submission information, and NHANES III population statistics. Data were extracted from studies of lipid-lowering therapy to modify low-density lipoprotein (LDL) levels for primary and secondary prevention of coronary heart disease. The data that were evaluated included sample size, study design, therapeutic intervention, length of study, percentage change in LDL levels, and patient demographics. Cumulative frequency curves of the LDL distribution among the US adult population were constructed. The mean efficacy of drug therapy from qualified studies was used to extrapolate the percentage of the population expected to respond to the intervention and to forecast the patient outcome. A useful tool for clinicians was constructed to approximate the percentage of patients, based on risk stratification, who would reach NCEP target goal after a given pharmacotherapeutic intervention to decrease LDL levels.

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats.

PubMed

Fujioka, Masaki; Gi, Min; Kawachi, Satoko; Tatsumi, Kumiko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

2016-11-01

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMA V ) is a major urinary metabolite of sodium arsenite (iAs III ) and induces urinary bladder cancers in rats. DMA V and iAs III are negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMA V and iAs III in rat urinary bladder epithelium and liver using gpt delta F344 rats. Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0, 92mg/L DMA V , or 87mg/L iAs III (each 50mg/L As) for 13weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection (gpt assay) and deletion mutations are identified in the red/gam genes by Spi - selection (Spi - assay). Results of the gpt and Spi - assays showed that DMA V and iAs III had no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMA V and iAs III are not mutagenic in urinary bladder epithelium or liver in rats. Copyright © 2016. Published by Elsevier B.V.

Maximizing Patient Recruitment and Retention in a Secondary Stroke Prevention Clinical Trial: Lessons Learned from the STAND FIRM Study.

PubMed

Thayabaranathan, Tharshanah; Cadilhac, Dominique A; Srikanth, Velandai K; Fitzgerald, Sharyn M; Evans, Roger G; Kim, Joosup; Gerraty, Richard P; Phan, Thanh G; Bladin, Christopher F; Nelson, Mark R; Frayne, Judith H; Thrift, Amanda G

2016-06-01

Recruitment and retention of patients in a clinical trial is important for generalizability and robustness of findings. We aimed to investigate features of a study design that were associated with recruitment and retention in a Phase II and Phase III trial of a secondary prevention program for stroke. Following informed consent in hospital, Phase II participants were randomized to intervention or usual care. Baseline clinical assessments were conducted at home approximately 3 months after discharge. In Phase III study, informed consent was obtained at home. We compared the characteristics of participants recruited and retained to 12 months for both phases. Interviews with study nurses were undertaken in order to ascertain their opinions of features of study design. Triangulation was used to identify the features of study design that nurses thought had improved recruitment and retention. All 24 eligible participants were recruited to the Phase II pilot study (100% recruitment), with 67% retention at 12 months. In Phase III study, 570 participants were recruited, and 93% of these participants had reached their 12-month assessment (n = 532) and were still participating. Consistent with the greater patient retention in Phase III study, nurses reported that patients' willingness to participate was greater when consent was obtained at home. Following a change in the consent process from hospital to home, more participants continued participation to 12 months. Pilot studies can provide important data to improve study design and better understand potential barriers to recruitment and retention. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Comparison of temporomandibular joint and ramus morphology between class II and class III cases before and after bi-maxillary osteotomy.

PubMed

Iguchi, Ran; Yoshizawa, Kunio; Moroi, Akinori; Tsutsui, Takamitsu; Hotta, Asami; Hiraide, Ryota; Takayama, Akihiro; Tsunoda, Tatsuya; Saito, Yuki; Sato, Momoko; Baba, Nana; Ueki, Koichiro

2017-12-01

The purpose of this study was to compare changes in temporomandibular joint (TMJ) and ramus morphology between class II and III cases before and after sagittal split ramus osteotomy (SSRO) and Le Fort I osteotomy. The subjects were 39 patients (78 sides) who underwent bi-maxillary surgery. They consisted of 2 groups (18 class II cases and 21 class III cases), and were selected randomly from among patients who underwent surgery between 2012 and 2016. The TMJ disc tissue and joint effusion were assessed by magnetic resonance imaging (MRI) and the TMJ space, condylar height, ramus height, ramus inclination and condylar square were assessed by computed tomography (CT), pre- and post-operatively. The number of joints with anterior disc displacement in class II was significantly higher than that in class III (p < 0.0001). However, there were no significant differences between the two classes regarding ratio of joint symptoms and ratio of joint effusion pre- and post-operatively. Class II was significantly better than class III regarding reduction ratio of condylar height (p < 0.0001) and square (p = 0.0005). The study findings suggest that condylar morphology could change in both class II and III after bi-maxillary surgery. The findings of the numerical analysis also demonstrated that reduction of condylar volume occurred frequently in class II, although TMJ disc position classification did not change significantly, as previously reported. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec.

PubMed

Walker, Dave; Ng Kwet Shing, Richard; Jones, Deborah; Gruss, Hans-Jurgen; Reguła, Jarosław

2015-01-01

Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD). Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20 mg) or Losec (20 mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes). Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0-30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns. Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with clinical effect in GERD therapy, highlighting the significance of several technical considerations for studies of this type. ClinicalTrials.gov NCT01493089.

Challenges of Correlating pH Change with Relief of Clinical Symptoms in Gastro Esophageal Reflux Disease: A Phase III, Randomized Study of Zegerid versus Losec

PubMed Central

Walker, Dave; Ng Kwet Shing, Richard; Jones, Deborah; Gruss, Hans-Jurgen; Reguła, Jarosław

2015-01-01

Background Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD). Methods Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20mg) or Losec (20mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes). Results Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0–30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns. Conclusions Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with clinical effect in GERD therapy, highlighting the significance of several technical considerations for studies of this type. Trial registration ClinicalTrials.gov NCT01493089 PMID:25706883

Emergency department-initiated palliative care for advanced cancer patients: protocol for a pilot randomized controlled trial.

PubMed

Kandarian, Brandon; Morrison, R Sean; Richardson, Lynne D; Ortiz, Joanna; Grudzen, Corita R

2014-06-25

For patients with advanced cancer, visits to the emergency department (ED) are common. Such patients present to the ED with a specific profile of palliative care needs, including burdensome symptoms such as pain, dyspnea, or vomiting that cannot be controlled in other settings and a lack of well-defined goals of care. The goals of this study are: i) to test the feasibility of recruiting, enrolling, and randomizing patients with serious illness in the ED; and ii) to evaluate the impact of ED-initiated palliative care on health care utilization, quality of life, and survival. This is a protocol for a single center parallel, two-arm randomized controlled trial in ED patients with metastatic solid tumors comparing ED-initiated palliative care referral to a control group receiving usual care. We plan to enroll 125 to 150 ED-advanced cancer patients at Mount Sinai Hospital in New York, USA, who meet the following criteria: i) pass a brief cognitive screen; ii) speak fluent English or Spanish; and iii) have never been seen by palliative care. We will use balanced block randomization in groups of 50 to assign patients to the intervention or control group after completion of a baseline questionnaire. All research staff performing assessment or analysis will be blinded to patient assignment. We will measure the impact of the palliative care intervention on the following outcomes: i) timing and rate of palliative care consultation; ii) quality of life and depression at 12 weeks, measured using the FACT-G and PHQ-9; iii) health care utilization; and iv) length of survival. The primary analysis will be based on intention-to-treat. This pilot randomized controlled trial will test the feasibility of recruiting, enrolling, and randomizing patients with advanced cancer in the ED, and provide a preliminary estimate of the impact of palliative care referral on health care utilization, quality of life, and survival. Clinical Trials.gov identifier: NCT01358110 (Entered 5/19/2011).

The Great Smoky Mountains Study of Youth. Goals, design, methods, and the prevalence of DSM-III-R disorders.

PubMed

Costello, E J; Angold, A; Burns, B J; Stangl, D K; Tweed, D L; Erkanli, A; Worthman, C M

1996-12-01

The Great Smoky Mountains Study of youth focuses on the relationship between the development of psychiatric disorder and the need for and use of mental health services. A multistage, overlapping cohorts design was used, in which 4500 of the 11758 children aged 9, 11, and 13 years in an 11-county area of the southeastern United States were randomly selected for screening for psychiatric symptoms. Children who scored in the top 25% on the screening questionnaire, together with a 1 in 10 random sample of the rest, were recruited for 4 waves of intensive, annual interviews (n = 1015 at wave 1). In a parallel study, all American Indian children aged 9, 11, and 13 years were recruited (N = 323 at wave 1). The 3-month prevalence (+/-SE) of any DSM-III-R axis I disorder in the main sample, weighted to reflect population prevalence rates, was 20.3% +/- 1.7%. The most common diagnoses were anxiety disorders (5.7% +/- 1.0%), enuresis (5.1% +/- 1.0%), tic disorders (4.2% +/- 0.9%), conduct disorder (3.3% +/- 0.6%), oppositional defiant disorder (2.7% +/- 0.4%), and hyperactivity (1.9% +/- 0.4%). The prevalence of psychiatric disorder in this rural sample was similar to rates reported in other recent studies. Poverty was the strongest demographic correlate of diagnosis, in both urban and rural children.

Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting.

PubMed

Uc, Ergun Y; Doerschug, Kevin C; Magnotta, Vincent; Dawson, Jeffrey D; Thomsen, Teri R; Kline, Joel N; Rizzo, Matthew; Newman, Sara R; Mehta, Sonya; Grabowski, Thomas J; Bruss, Joel; Blanchette, Derek R; Anderson, Steven W; Voss, Michelle W; Kramer, Arthur F; Darling, Warren G

2014-07-29

To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p < 0.05 to p < 0.001). Increase in maximum oxygen consumption correlated with improvements on the flanker task and quality of life (p < 0.05). Our preliminary study suggests that aerobic walking in a community setting is safe, well tolerated, and improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD. This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition. © 2014 American Academy of Neurology.

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

PubMed

Borstlap, W A A; Buskens, C J; Tytgat, K M A J; Tuynman, J B; Consten, E C J; Tolboom, R C; Heuff, G; van Geloven, N; van Wagensveld, B A; C A Wientjes, C A; Gerhards, M F; de Castro, S M M; Jansen, J; van der Ven, A W H; van der Zaag, E; Omloo, J M; van Westreenen, H L; Winter, D C; Kennelly, R P; Dijkgraaf, M G W; Tanis, P J; Bemelman, W A

2015-06-28

At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. ClincalTrials.gov: NCT02243735 .

Ternary AlGaN Alloys with High Al Content and Enhanced Compositional Homogeneity Grown by Plasma-Assisted Molecular Beam Epitaxy

NASA Astrophysics Data System (ADS)

Fellmann, Vincent; Jaffrennou, Périne; Sam-Giao, Diane; Gayral, Bruno; Lorenz, Katharina; Alves, Eduardo; Daudin, Bruno

2011-03-01

We have studied the influence of III/N flux ratio and growth temperature on structural and optical properties of high Al-content, around 50-60%, AlGaN alloy layers grown by plasma-assisted molecular beam epitaxy. In a first part, based on structural analysis by Rutherford Backscattering Spectroscopy, we establish that a III/N flux ratio slightly above 1 produces layers with low amount of structural defects. In a second part, we study the effect of growth temperature on structural and optical properties of layers grown with previously determined optimal III/N flux ratio. We find that optimal growth temperatures for Al0.50Ga0.50N layers with compositional homogeneity related with narrow UV photoluminescence properties are in the low temperature range for growing GaN layers, i.e., 650-680 °C. We propose that lowering Ga adatom diffusion on the surface favors random incorporation of both Ga and Al adatoms on wurtzite crystallographic sites leading to the formation of an homogeneous alloy.

Early orthodontic treatment for Class III malocclusion: A systematic review and meta-analysis.

PubMed

Woon, See Choong; Thiruvenkatachari, Badri

2017-01-01

Class III malocclusion affects between 5% and 15% of our population. The 2 most common dilemmas surrounding Class III treatment are the timing of treatment and the type of appliance. A number of appliances have been used to correct a Class III skeletal discrepancy, but there is little evidence available on their effectiveness in the long term. Similarly, early treatment of Class III malocclusion has been practiced with increasing interest. However, there has been no solid evidence on the benefits in the long term. The aim of this systematic review was to evaluate the effectiveness of orthodontic/orthopedic methods used in the early treatment of Class III malocclusion in the short and long terms. Several sources were used to identify all relevant studies independently of language. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase (Ovid), and MEDLINE (Ovid) were searched to June 2016. The selection criteria included randomized controlled trials (RCTs) and prospective controlled clinical trials (CCTs) of children between the ages of 7 and 12 years on early treatment with any type of orthodontic/orthopedic appliance compared with another appliance to correct Class III malocclusion or with an untreated control group. The primary outcome measure was correction of reverse overjet, and the secondary outcomes included skeletal changes, soft tissue changes, quality of life, patient compliance, adverse effect, Peer Assessment Rating score, and treatment time. The search results were screened for inclusion, and the data extracted by 2 independent authors. The data were analyzed using software (version 5.1, Review Manager; The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen, Denmark). The mean differences with 95% confidence intervals were expressed for the continuous data. Random effects were carried out with high levels of clinical or statistical heterogeneity and fixed affects when the heterogeneity was low. Fifteen studies, 9 RCTs and 6 CCTs, were included in this review. In the RCT group, only 3 of 9 studies were assessed at low risk of bias, and the others were at high or unclear risk of bias. All 6 CCT studies were classified as high risk of bias. Three RCTs involving 141 participants looked at the comparison between protraction facemask and untreated control. The results for reverse overjet (mean difference, 2.5 mm; 95% CI, 1.21-3.79; P = 0.0001) and ANB angle (mean difference, 3.90°; 95% CI, 3.54-4.25; P <0.0001) were statistically significant favoring the facemask group. All CCTs demonstrated a statistically significant benefit in favor of the use of each appliance. However, the studies had high risk of bias. There is a moderate amount of evidence to show that early treatment with a facemask results in positive improvement for both skeletal and dental effects in the short term. However, there was lack of evidence on long-term benefits. There is some evidence with regard to the chincup, tandem traction bow appliance, and removable mandibular retractor, but the studies had a high risk of bias. Further high-quality, long-term studies are required to evaluate the early treatment effects for Class III malocclusion patients. PROSPERO CRD42015024252. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

PubMed

Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D

2015-03-24

Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist. Copyright © 2015 Elsevier Ltd. All rights reserved.

Utilizing findings from the APACHE III research to develop operational information system for the ICU--the APACHE III ICU Management System.

PubMed Central

Knaus, W. A.; Draper, E. A.; Wagner, D. P.

1991-01-01

The APACHE III data base reflects the disease, physiologic status, and outcome data from 17,400 ICU patients at 40 hospitals, 26 of which were randomly selected from representative geographic regions, bed size, and teaching status. This provides a nationally representative standard for measuring several important aspects of ICU performance. Results from the study have now been used to develop an automated information system to provide real time information about expected ICU patient outcome, length of stay, production cost, and ICU performance. The information system provides several new capabilities to ICU clinicians, clinic, and hospital administrators. Among the system's capabilities are: the ability to compare local ICU performance against predetermined criteria; the ability to forecast nursing requirements; and, the ability to make both individual and group patient outcome predictions. The system also provides improved administrative support by tracking ICU charges at the point of origin and reduces staff workload eliminating the requirement for several manually maintained logs and patient lists. APACHE III has the capability to electronically interface with and utilize data already captured in existing hospital information systems, automated laboratory information systems, and patient monitoring systems. APACHE III will also be completely integrated with several CIS vendors' products. PMID:1807779

Modified Angle's Classification for Primary Dentition.

PubMed

Chandranee, Kaushik Narendra; Chandranee, Narendra Jayantilal; Nagpal, Devendra; Lamba, Gagandeep; Choudhari, Purva; Hotwani, Kavita

2017-01-01

This study aims to propose a modification of Angle's classification for primary dentition and to assess its applicability in children from Central India, Nagpur. Modification in Angle's classification has been proposed for application in primary dentition. Small roman numbers i/ii/iii are used for primary dentition notation to represent Angle's Class I/II/III molar relationships as in permanent dentition, respectively. To assess applicability of modified Angle's classification a cross-sectional preschool 2000 children population from central India; 3-6 years of age residing in Nagpur metropolitan city of Maharashtra state were selected randomly as per the inclusion and exclusion criteria. Majority 93.35% children were found to have bilateral Class i followed by 2.5% bilateral Class ii and 0.2% bilateral half cusp Class iii molar relationships as per the modified Angle's classification for primary dentition. About 3.75% children had various combinations of Class ii relationships and 0.2% children were having Class iii subdivision relationship. Modification of Angle's classification for application in primary dentition has been proposed. A cross-sectional investigation using new classification revealed various 6.25% Class ii and 0.4% Class iii molar relationships cases in preschool children population in a metropolitan city of Nagpur. Application of the modified Angle's classification to other population groups is warranted to validate its routine application in clinical pediatric dentistry.

Are manual therapies, passive physical modalities, or acupuncture effective for the management of patients with whiplash-associated disorders or neck pain and associated disorders? An update of the Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders by the OPTIMa collaboration.

PubMed

Wong, Jessica J; Shearer, Heather M; Mior, Silvano; Jacobs, Craig; Côté, Pierre; Randhawa, Kristi; Yu, Hainan; Southerst, Danielle; Varatharajan, Sharanya; Sutton, Deborah; van der Velde, Gabrielle; Carroll, Linda J; Ameis, Arthur; Ammendolia, Carlo; Brison, Robert; Nordin, Margareta; Stupar, Maja; Taylor-Vaisey, Anne

2016-12-01

In 2008, the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders (Neck Pain Task Force) found limited evidence on the effectiveness of manual therapies, passive physical modalities, or acupuncture for the management of whiplash-associated disorders (WAD) or neck pain and associated disorders (NAD). This review aimed to update the findings of the Neck Pain Task Force, which examined the effectiveness of manual therapies, passive physical modalities, and acupuncture for the management of WAD or NAD. This is a systematic review and best evidence synthesis. The sample includes randomized controlled trials, cohort studies, and case-control studies comparing manual therapies, passive physical modalities, or acupuncture with other interventions, placebo or sham, or no intervention. The outcome measures were self-rated or functional recovery, pain intensity, health-related quality of life, psychological outcomes, or adverse events. We systematically searched five databases from 2000 to 2014. Random pairs of independent reviewers critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a low risk of bias were stratified by the intervention's stage of development (exploratory vs. evaluation) and synthesized following best evidence synthesis principles. Funding was provided by the Ministry of Finance. We screened 8,551 citations, and 38 studies were relevant and 22 had a low risk of bias. Evidence from seven exploratory studies suggests that (1) for recent but not persistent NAD grades I-II, thoracic manipulation offers short-term benefits; (2) for persistent NAD grades I-II, technical parameters of cervical mobilization (eg, direction or site of manual contact) do not impact outcomes, whereas one session of cervical manipulation is similar to Kinesio Taping; and (3) for NAD grades I-II, strain-counterstrain treatment is no better than placebo. Evidence from 15 evaluation studies suggests that (1) for recent NAD grades I-II, cervical and thoracic manipulation provides no additional benefit to high-dose supervised exercises, and Swedish or clinical massage adds benefit to self-care advice; (2) for persistent NAD grades I-II, home-based cupping massage has similar outcomes to home-based muscle relaxation, low-level laser therapy (LLLT) does not offer benefits, Western acupuncture provides similar outcomes to non-penetrating placebo electroacupuncture, and needle acupuncture provides similar outcomes to sham-penetrating acupuncture; (3) for WAD grades I-II, needle electroacupuncture offers similar outcomes as simulated electroacupuncture; and (4) for recent NAD grades III, a semi-rigid cervical collar with rest and graded strengthening exercises lead to similar outcomes, and LLLT does not offer benefits. Our review adds new evidence to the Neck Pain Task Force and suggests that mobilization, manipulation, and clinical massage are effective interventions for the management of neck pain. It also suggests that electroacupuncture, strain-counterstrain, relaxation massage, and some passive physical modalities (heat, cold, diathermy, hydrotherapy, and ultrasound) are not effective and should not be used to manage neck pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of the PANVAC-VF vaccine for pancreatic cancer.

PubMed

Petrulio, Christian A; Kaufman, Howard L

2006-02-01

PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. Vaccination is administered by subcutaneous injection followed by 4 days of local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at the vaccination site. The vaccine has been developed for patients with advanced pancreatic cancer and has now entered a randomized Phase III clinical trial. This review will describe the background of recombinant poxvirus technology for tumor vaccine development, detail the key preclinical studies supporting the regimen, review the clinical trials supporting the current Phase III study, and highlight the key challenges and future obstacles to successful implementation of PANVAC-VF for pancreatic cancer.

[Clinical policy for management and risk stratification of community-acquired pneumonia in patients hospitalized on the basis of conventional admission criteria].

PubMed

Putinati, Stefano; Ballerin, Licia; Piattella, Marco; Ritrovato, Lucia; Zabini, Franco; Potena, Alfredo

2003-05-01

To identify discrepancies between Pneumonia Severity Index (PSI) risk class and the conventional criteria for deciding the site of care we performed a prospective observational study on 229 patients hospitalized for community-acquired pneumonia. PSI classes and corresponding mortality rates were as following: class I, 41 patients (0%); class II, 20 (0%); class III, 58 (1.7%); class IV, 86 (8.1%); class V, 24 (33.3%). Overall, 119 patients (52%) who were hospitalized according to conventional criteria were assigned to low-risk classes (I-III). Among these low risk patients, 58 (49%) had complications as respiratory failure, pleural effusion, hypotension or shock; among remaining patients, no reasons for admission were found. This latter group deserves prospective evaluation in randomized studies comparing in-hospital versus outpatient management.

A tutorial on pilot studies: the what, why and how

PubMed Central

2010-01-01

Pilot studies for phase III trials - which are comparative randomized trials designed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas. Also commonly know as "feasibility" or "vanguard" studies, they are designed to assess the safety of treatment or interventions; to assess recruitment potential; to assess the feasibility of international collaboration or coordination for multicentre trials; to increase clinical experience with the study medication or intervention for the phase III trials. They are the best way to assess feasibility of a large, expensive full-scale study, and in fact are an almost essential pre-requisite. Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies. The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including: 1) the general reasons for conducting a pilot study; 2) the relationships between pilot studies, proof-of-concept studies, and adaptive designs; 3) the challenges of and misconceptions about pilot studies; 4) the criteria for evaluating the success of a pilot study; 5) frequently asked questions about pilot studies; 7) some ethical aspects related to pilot studies; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format. PMID:20053272

Deep Brain Stimulation for Early Stage Parkinson's Disease: An Illustrative Case

PubMed Central

Gill, Chandler E.; Allen, Laura A.; Konrad, Peter E.; Davis, Thomas L.; Bliton, Mark J.; Finder, Stuart G.; Tramontana, Michael G.; Kao, C. Chris; Remple, Michael S.; Bradenham, Courtney H.; Charles, P. David

2011-01-01

Objectives Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective intervention in advanced Parkinson's Disease (PD), but its efficacy and safety in early PD are unknown. Our team is conducting a randomized pilot trial investigating DBS in early PD. This report describes one participant who received bilateral STN-DBS. Materials/Methods Thirty subjects have been randomized to either optimal drug therapy (ODT) or DBS + ODT. Microelectrode recordings from the STN and substantia nigra (SN) are collected at implantation. The Unified Parkinson's Disease Rating Scale Motor Subscale (UPDRS-III) is administered in the ON and OFF states semi-annually and neuropsychological function and quality of life are assessed annually. We describe a 54-year-old man with a two-year history of PD who was randomized to DBS + ODT and followed for two years. Results The subject showed a lower STN to SN ratio of neuronal activity than advanced PD patients, and higher firing rate than non-PD patients. The subject's ON total UPDRS and UPDRS-III scores improved during the two-year follow-up, while his OFF UPDRS-III score and levodopa equivalent daily dose (LEDD) increased. Quality of life, verbal fluency and verbal learning improved. He did not experience any serious adverse events. Conclusions This report details the first successful application of bilateral STN DBS for early stage PD during a clinical trial. PMID:21939467

Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial

PubMed Central

Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

2015-01-01

The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival. PMID:26219568

Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial.

PubMed

Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

2015-07-29

The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice's four criteria. The Spearman's rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice's second criterion. Being consistent with all Prentice's criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival.

Modeling Laser Damage Thresholds Using the Thompson-Gerstman Model

DTIC Science & Technology

2014-10-01

Gerstman model was intended to be a modular tool fit for integration into other computational models. This adds usability to the standalone code...Advanced Study Institute, Series A – Life Sciences, Vol. 34, pp. 77-97. New York: Plenum Press . 4. Birngruber, R., V.-P. Gabel and F. Hillenkamp...Random granule placement - varies with melnum. ; ii. Depth averaging or shadowing - varies with melnum. ; iii. T(r,t) single granule calc

Acupuncture in Treating Dry Mouth Caused By Radiation Therapy in Patients With Head and Neck Cancer | Division of Cancer Prevention

Cancer.gov

RATIONALE: Acupuncture may help relieve dry mouth caused by radiation therapy. PURPOSE: This randomized phase III trial is studying to see how well one set of acupuncture points work in comparison to a different set of acupuncture points or standard therapy in treating dry mouth caused by radiation therapy in patients with head and neck cancer. |

A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hille, Andrea; Schmidberger, Heinz; Hermann, Robert M.

2005-12-01

Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo andmore » the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.« less

Impact of Tight Glycemic Control on Neurodevelopmental Outcomes at 1 Year of Age for Children with Congenital Heart Disease: A Randomized Controlled Trial

PubMed Central

Sadhwani, Anjali; Asaro, Lisa A.; Goldberg, Caren; Ware, Janice; Butcher, Jennifer; Gaies, Michael; Smith, Cynthia; Alexander, Jamin L.; Wypij, David; Agus, Michael S. D.

2016-01-01

Objective To assess the association of postoperative tight glycemic control and hypoglycemia in children undergoing cardiac surgery with neurodevelopmental outcomes at 1 year of age. Study design A 2-center, prospective, randomized trial of postoperative tight glycemic control vs standard care was conducted in 980 children undergoing cardiac surgery. Neurodevelopmental outcomes were assessed at nine to 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Adaptive Behavior Assessment System, Second Edition, the Ages and Stages Questionnaire, Third Edition, and the Brief Infant Toddler Social-Emotional Assessment. Results Neurodevelopmental follow-up was performed on 237 patients with a mean age of 13 months. No significant treatment group differences were found in the Bayley-III and Adaptive Behavior Assessment System, Second Edition composite scores or percentage at risk based on the Ages and Stages Questionnaire, Third Edition and the Brief Infant Toddler Social-Emotional Assessment. Patients who experienced moderate to severe hypoglycemia (n = 8) had lower Bayley-III composite scores compared with patients with no to mild hypoglycemia, even after controlling for factors known to be associated with poorer neurodevelopmental outcomes. Conclusion For infants undergoing cardiac surgery, tight glycemic control did not impact neurodevelopmental outcomes compared with standard care. These data suggest a possible association between moderate to severe hypoglycemia and poorer neurodevelopmental outcomes at 1 year of age. PMID:27112038

Polyurethane on titanium unconstrained disc arthroplasty versus anterior discectomy and fusion for the treatment of cervical disc disease: a review of level I-II randomized clinical trials including clinical outcomes.

PubMed

Aragonés, María; Hevia, Eduardo; Barrios, Carlos

2015-12-01

To contrast the clinical and radiologic outcomes and adverse events of anterior cervical discectomy and fusion (ACDF) with a single cervical disc arthroplasty design, the polyurethane on titanium unconstrained cervical disc (PTUCD). This is a systematic review of randomized clinical trials (RCT) with evidence level I-II reporting clinical outcomes. After a search on different databases including PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE, a total of 10 RCTs out of 51 studies found were entered in the study. RTCs were searched from the earliest available records in 2005 to November 2014. Out of a total of 1101 patients, 562 were randomly assigned into the PTUCD arthroplasty group and 539 into the ACDF group. The mean follow-up was 30.9 months. Patients undergoing arthroplasty had lower Neck Disability Index, and better SF-36 Physical component scores than ACDF patients. Patients with PTUCD arthroplasty had also less radiological degenerative changes at the upper adjacent level. Overall adverse events were twice more frequent in patients with ACDF. The rate of revision surgery including both adjacent and index level was slightly higher in patients with ACDF, showing no statistically significant difference. According to this review, PTUCD arthroplasty showed a global superiority to ACDF in clinical outcomes. The impact of both surgical techniques on the cervical spine (radiological spine deterioration and/or complications) was more severe in patients undergoing ACDF. However, the rate of revision surgeries at any cervical level was equivalent for ACDF and PTUCD arthroplasty.

A meta-analysis of phase III randomized controlled trials with novel oral anticoagulants in atrial fibrillation: comparisons between direct thrombin inhibitors vs. factor Xa inhibitors and different dosing regimens.

PubMed

Providência, Rui; Grove, Erik Lerkevang; Husted, Steen; Barra, Sérgio; Boveda, Serge; Morais, João

2014-12-01

Previous studies evaluating the ability of novel oral anticoagulants (NOAC) to prevent thromboembolism in patients with non-valvular atrial fibrillation (AF) have identified differences between the efficacy and safety of the drugs tested. Whether these differences reflect differences in direct thrombin or Xa inhibition, different dosing regimens or specific aspects of each agent or trial has not yet been explored. A search was performed on MEDLINE, EMBASE and COCHRANE, and ongoing studies were tracked on clinicaltrials.gov. Phase III randomized controlled trials of direct thrombin inhibitors (DTI) and factor Xa inhibitors (FXaI) vs. warfarin in patients with AF were eligible. Data were pooled using random-effects, according to the Mantel-Haenszel model. Sensitivity analyses were performed on DTI, FXaI, once-daily and twice-daily regimens. Seven studies were pooled, including a total of 80,290 patients. Both DTI and FXaI outperformed warfarin regarding stroke or systemic embolism, intracranial bleeding, total and cardiovascular mortality. No significant differences were found between DTI and FXaI or between once-daily and twice-daily regimens. Some drugs performed worse than warfarin regarding some secondary endpoints, including: edoxaban 30 mg bid on ischaemic stroke, dabigatran on acute myocardial infarction, dabigatran 150 mg bid and rivaroxaban 20mgod on gastrointestinal bleeding. Our pooled data do not support the hypothesis of a significant class-effect of DTI or FXaI, nor the benefit of once-daily vs. twice-daily dosing in the setting of AF, reinforcing that the choice of NOAC should be adapted to the specific patient and focused on the agent itself, rather than the pharmacological class or dosing regimen.

Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

PubMed Central

Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

2013-01-01

Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

Abagovomab As Maintenance Therapy in Patients With Epithelial Ovarian Cancer: A Phase III Trial of the AGO OVAR, COGI, GINECO, and GEICO—The MIMOSA Study

PubMed Central

Sabbatini, Paul; Harter, Philipp; Scambia, Giovanni; Sehouli, Jalid; Meier, Werner; Wimberger, Pauline; Baumann, Klaus H.; Kurzeder, Christian; Schmalfeldt, Barbara; Cibula, David; Bidzinski, Mariusz; Casado, Antonio; Martoni, Andrea; Colombo, Nicoletta; Holloway, Robert W.; Selvaggi, Luigi; Li, Andrew; del Campo, Jose; Cwiertka, Karel; Pinter, Tamas; Vermorken, Jan B.; Pujade-Lauraine, Eric; Scartoni, Simona; Bertolotti, Monica; Simonelli, Cecilia; Capriati, Angela; Maggi, Carlo Alberto; Berek, Jonathan S.; Pfisterer, Jacobus

2013-01-01

Purpose To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients with ovarian cancer in first clinical remission. Patients and Methods Patients with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer in complete clinical remission after primary surgery and platinum- and taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a phase III, double-blind, placebo-controlled, multicenter study. Abagovomab 2 mg or placebo was administered as 1-mL suspension once every 2 weeks for 6 weeks (induction phase) and then once every 4 weeks (maintenance phase) until recurrence or up to 21 months after random assignment of the last patient. The primary end point was RFS; secondary end points were OS and immunologic response. Results Characteristics of the 888 patients included: mean age, 56.3 years; Eastern Cooperative Oncology Group performance status, ≤ 1 in > 99% of patients; serous papillary subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35U/mL after third cycle, 80.9%. Mean exposure to study treatment (± standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS for the treatment group using tumor size categorization (≤ 1 cm, > 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P = .322). The most frequently reported type of adverse event was an injection site reaction in 445 patients (50.2%), followed by injection site erythema and fatigue in 227 (25.6%) and 212 patients (23.9%), respectively. By the final visit, median anti–anti-idiotypic antibody level was 493,000.0 ng/mL, indicating a robust response. Conclusion Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS. PMID:23478059

High-Throughput Analysis of Age-Dependent Protein Changes in Layer II/III of the Human Orbitofrontal Cortex

NASA Astrophysics Data System (ADS)

Kapadia, Fenika

Studies on the orbitofrontal cortex (OFC) during normal aging have shown a decline in cognitive functions, a loss of spines/synapses in layer III and gene expression changes related to neural communication. Biological changes during the course of normal aging are summarized into 9 hallmarks based on aging in peripheral tissue. Whether these hallmarks apply to non-dividing brain tissue is not known. Therefore, we opted to perform large-scale proteomic profiling of the OFC layer II/III during normal aging from 15 young and 18 old male subjects. MaxQuant was utilized for label-free quantification and statistical analysis by the Random Intercept Model (RIM) identified 118 differentially expressed (DE) age-related proteins. Altered neural communication was the most represented hallmark of aging (54% of DE proteins), highlighting the importance of communication in the brain. Functional analysis showed enrichment in GABA/glutamate signaling and pro-inflammatory responses. The former may contribute to alterations in excitation/inhibition, leading to cognitive decline during aging.

Temporomandibular disorders in growing patients after treatment of class II and III malocclusion with orthopaedic appliances: a systematic review.

PubMed

Jiménez-Silva, Antonio; Carnevali-Arellano, Romano; Venegas-Aguilera, Matías; Tobar-Reyes, Julio; Palomino-Montenegro, Hernán

2018-05-01

To determine if the use of orthopaedic appliances in growing patients applied to correct Class II and III malocclusion is related to the development of temporomandibular disorders (TMD). A systematic review was conducted between 1960 and July 2017, based on electronic databases: PubMed, Cochrane Library, Embase, Medline, Scopus, EBSCOhost, Scielo, Lilacs and Bireme. Controlled clinical trials (CCTs) and randomized controlled trials (RCTs) were identified. The articles were selected and analyzed by two authors independently. The quality of the evidence was determined according to the guidelines of the Cochrane Risk Bias Assessment Tool and the Cochrane Quality Study Guide. Seven articles were included, four CCTs and three RCTs. The studies were grouped according to malocclusion treatment in (a) class II appliances (n = 4) and (b) class III appliances (n = 3). The quality of evidence was low due to the high risk of bias, independent of the association reported. All studies concluded that the use of orthopaedic appliances would not contribute to the development of TMD. The quality of evidence available is insufficient to establish definitive conclusions, since the studies were very heterogeneous and presented a high risk of bias. However, it is suggested that the use of orthopaedic appliances to correct class II and III malocclusion in growing patients would not be considered as a risk factor for the development of TMD. High-quality RCTs are required to draw any definitive conclusions.

[Cell-ELA-based determination of binding affinity of DNA aptamer against U87-EGFRvIII cell].

PubMed

Tan, Yan; Liang, Huiyu; Wu, Xidong; Gao, Yubo; Zhang, Xingmei

2013-05-01

A15, a DNA aptamer with binding specificity for U87 glioma cells stably overexpressing the epidermal growth factor receptor variant III (U87-EGFRvIII), was generated by cell systematic evolution of ligands by exponential enrichment (cell-SELEX) using a random nucleotide library. Subsequently, we established a cell enzyme-linked assay (cell-ELA) to detect the affinity of A15 compared to an EGFR antibody. We used A15 as a detection probe and cultured U87-EGFRvIII cells as targets. Our data indicate that the equilibrium dissociation constants (K(d)) for A15 were below 100 nmol/L and had similar affinity compared to an EGFR antibody for U87-EGFRvIII. We demonstrated that the cell-ELA was a useful method to determine the equilibrium dissociation constants (K(d)) of aptamers generated by cell-SELEX.

Deinfibulation for treating urologic complications of type III female genital mutilation: A systematic review.

PubMed

Effa, Emmanuel; Ojo, Olumuyiwa; Ihesie, Austin; Meremikwu, Martin M

2017-02-01

Women and girls who have undergone type III female genital mutilation (FGM) may suffer urologic complications such as recurrent urinary tract infections, obstruction, stones, and incontinence. To assess the effectiveness of deinfibulation for preventing and treating urologic complications in women and girls living with FGM. The following major databases were searched from inception to August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, SCOPUS, Web of Science, and ClinicalTrials.gov without language restrictions. Randomized controlled studies (RCTs) or observational studies with controls were considered. We screened the results of the search independently for potentially relevant studies and applied inclusion and exclusion criteria for the full texts of the relevant studies. No RCTs were found. We found three case reports and a retrospective case review, all of which were excluded. There is no evidence on the use of deinfibulation to improve urologic complications among women with type III FGM. Current clinical practice may be informed by anecdotal evidence from case reports. Appropriate RCTs and observational studies with comparison groups in countries where FGM is common are needed. PROSPERO registration: CRD42015024901. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

The Effect of Holly Quran Voice With and Without Translation on Stress, Anxiety and Depression During Pregnancy: A Randomized Controlled Trial.

PubMed

Jabbari, Batoul; Mirghafourvand, Mojgan; Sehhatie, Fahimeh; Mohammad-Alizadeh-Charandabi, Sakineh

2017-05-30

This study aimed to investigate the effect of Holy Quran on stress, anxiety and depression in Iranian pregnant women. A total of 168 participants were allocated randomly into three groups. Group I received broadcast of the Holy Quran with translation, group II received broadcast of the Holy Quran without translation, and group III was the control group. After intervention, scores of perceived stress, state anxiety, trait anxiety and depression in group I and group II were significantly lower compared with the control group. The Holly Quran with translation and without it, both are the effective for reducing stress, anxiety and depression during pregnancy.

Differentiation of functional constipation and constipation predominant irritable bowel syndrome based on Rome III criteria: a population-based study.

PubMed

Koloski, N A; Jones, M; Young, M; Talley, N J

2015-05-01

While the Rome III classification recognises functional constipation (FC) and constipation predominant IBS (IBS-C) as distinct disorders, recent evidence has suggested that these disorders are difficult to separate in clinical practice. To identify whether clinical and lifestyle factors differentiate Rome III-defined IBS-C from FC based on gastrointestinal symptoms and lifestyle characteristics. 3260 people randomly selected from the Australian population returned a postal survey. FC and IBS-C were defined according to Rome III. The first model used logistic regression to differentiate IBS-C from FC based on lifestyle, quality-of-life and psychological characteristics. The second approach was data-driven employing latent class analysis (LCA) to identify naturally occurring clusters in the data considering all symptoms involved in the Rome III criteria for IBS-C and FC. We found n = 206 (6.5%; 95% CI 5.7-7.4%) people met strict Rome III FC whereas n = 109 (3.5%; 95% CI 2.8-4.1%) met strict Rome III IBS-C. The case-control approach indicated that FC patients reported an older age at onset of constipation, were less likely to exercise, had higher mental QoL and less health care seeking than IBS-C. LCA yielded one latent class that was predominantly (75%) FC, while the other class was approximately half IBS-C and half FC. The FC-dominated latent class had clearly lower levels of symptoms used to classify IBS (pain-related symptoms) and was more likely to be male (P = 0.046) but was otherwise similar in distribution of lifestyle factors to the mixed class. The latent class analysis approach suggests a differentiation based more on symptom severity rather than the Rome III view. © 2015 John Wiley & Sons Ltd.

Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey.

PubMed

Arbes, Samuel J; Gergen, Peter J; Elliott, Leslie; Zeldin, Darryl C

2005-08-01

Allergy skin tests were administered in the second and third National Health and Nutrition Examination Surveys (NHANES II and III) conducted in the United States from 1976 through 1980 and 1988 through 1994, respectively. This study estimated positive skin test response rates in NHANES III and identified predictors of one or more positive test responses. Comparisons with NHANES II were also made. In NHANES III, 10 allergens and 2 controls were tested in all subjects aged 6 to 19 years and a random half-sample of subjects aged 20 to 59 years. A wheal-based definition of a positive test response was used. In NHANES III, 54.3% of the population had positive test responses to 1 or more allergens. Prevalences were 27.5% for dust mite, 26.9% for perennial rye, 26.2% for short ragweed, 26.1% for German cockroach, 18.1% for Bermuda grass, 17.0% for cat, 15.2% for Russian thistle, 13.2% for white oak, 12.9% for Alternaria alternata, and 8.6% for peanut. Among those with positive test responses, the median number of positive responses was 3.0. Adjusted odds of a positive test response were higher for the following variables: age of 20 to 29 years, male sex, minority race, western region, old homes, and lower serum cotinine levels. For the 6 allergens common to NHANES II and III, prevalences were 2.1 to 5.5 times higher in NHANES III. The majority of the US population represented in NHANES III was sensitized to 1 or more allergens. Whether the higher prevalences observed in NHANES III reflect true changes in prevalence or methodological differences between the surveys cannot be determined with certainty.

Performance of the score systems Acute Physiology and Chronic Health Evaluation II and III at an interdisciplinary intensive care unit, after customization

PubMed Central

Markgraf, Rainer; Deutschinoff, Gerd; Pientka, Ludger; Scholten, Theo; Lorenz, Cristoph

2001-01-01

Background: Mortality predictions calculated using scoring scales are often not accurate in populations other than those in which the scales were developed because of differences in case-mix. The present study investigates the effect of first-level customization, using a logistic regression technique, on discrimination and calibration of the Acute Physiology and Chronic Health Evaluation (APACHE) II and III scales. Method: Probabilities of hospital death for patients were estimated by applying APACHE II and III and comparing these with observed outcomes. Using the split sample technique, a customized model to predict outcome was developed by logistic regression. The overall goodness-of-fit of the original and the customized models was assessed. Results: Of 3383 consecutive intensive care unit (ICU) admissions over 3 years, 2795 patients could be analyzed, and were split randomly into development and validation samples. The discriminative powers of APACHE II and III were unchanged by customization (areas under the receiver operating characteristic [ROC] curve 0.82 and 0.85, respectively). Hosmer-Lemeshow goodness-of-fit tests showed good calibration for APACHE II, but insufficient calibration for APACHE III. Customization improved calibration for both models, with a good fit for APACHE III as well. However, fit was different for various subgroups. Conclusions: The overall goodness-of-fit of APACHE III mortality prediction was improved significantly by customization, but uniformity of fit in different subgroups was not achieved. Therefore, application of the customized model provides no advantage, because differences in case-mix still limit comparisons of quality of care. PMID:11178223

Active transport on disordered microtubule networks: the generalized random velocity model.

PubMed

Kahana, Aviv; Kenan, Gilad; Feingold, Mario; Elbaum, Michael; Granek, Rony

2008-11-01

The motion of small cargo particles on microtubules by means of motor proteins in disordered microtubule networks is investigated theoretically using both analytical tools and computer simulations. Different network topologies in two and three dimensions are considered, one of which has been recently studied experimentally by Salman [Biophys. J. 89, 2134 (2005)]. A generalization of the random velocity model is used to derive the mean-square displacement of the cargo particle. We find that all cases belong to the class of anomalous superdiffusion, which is sensitive mainly to the dimensionality of the network and only marginally to its topology. Yet in three dimensions the motion is very close to simple diffusion, with sublogarithmic corrections that depend on the network topology. When details of the thermal diffusion in the bulk solution are included, no significant change to the asymptotic time behavior is found. However, a small asymmetry in the mean microtubule polarity affects the corresponding long-time behavior. We also study a three-dimensional model of the microtubule network in living animal cells. Three first-passage-time problems of intracellular transport are simulated and analyzed for different motor processivities: (i) cargo that originates near the nucleus and has to reach the membrane, (ii) cargo that originates from the membrane and has to reach the nucleus, and (iii) cargo that leaves the nucleus and has to reach a specific target in the cytoplasm. We conclude that while a higher motor processivity increases the transport efficiency in cases (i) and (ii), in case (iii) it has the opposite effect. We conjecture that the balance between the different network tasks, as manifested in cases (i) and (ii) versus case (iii), may be the reason for the evolutionary choice of a finite motor processivity.

Immunogenicity and safety of a novel MMR vaccine (live, freeze-dried) containing the Edmonston-Zagreb measles strain, the Hoshino mumps strain, and the RA 27/3 rubella strain: Results of a randomized, comparative, active controlled phase III clinical trial.

PubMed

Sood, Ashwani; Mitra, Monjori; Joshi, Himanshu Arvind; Nayak, Uma Siddhartha; Siddaiah, Prashanth; Babu, T Ramesh; Mahapatro, Samarendra; Sanmukhani, Jayesh; Gupta, Gaurav; Mittal, Ravindra; Glueck, Reinhard

2017-07-03

This phase III clinical trial was conducted to evaluate the immunogenicity and safety of the single-dose and multi-dose formulations of a novel MMR vaccine (live, freeze-dried) developed by M/s Cadila Healthcare Limited, India (Cadila MMR vaccine), containing the Hoshino mumps strain, compared to that of an existing MMR vaccine (live, freeze-dried) developed by M/s Serum Institute of India Limited, India (Serum MMR vaccine). These two vaccines have similar measles and rubella strains, but different mumps strains (Hoshino in Cadila MMR vaccine, and L-Zagreb in Serum MMR vaccine). Three hundred and twenty-eight subjects of either sex, aged 15-18 months, were randomized in a 2:1 ratio to receive either the Cadila or Serum MMR vaccine. Immunogenicity assessments (IgG antibodies against measles, mumps, and rubella viruses) were done at baseline and 42 d after vaccination. Solicited (local and systemic) and unsolicited adverse events were recorded for up to 42 d following vaccination. The Cadila MMR vaccine was found to be non-inferior to the Serum MMR vaccine in terms of end-of-study proportion of subjects seropositive for anti-measles antibodies (100.0% in both groups), anti-mumps antibodies (94.5% vs. 94.0%), and anti-rubella antibodies (95.5% vs. 91.0%). Both vaccines were well tolerated by all study participants; the most common adverse event reported in both groups was fever, followed by rash. The results of this phase III clinical trial show that the novel Cadila MMR vaccine is non-inferior to the Serum MMR vaccine.

Effects of Single Low Dose of Dexamethasone before Noncardiac and Nonneurologic Surgery and General Anesthesia on Postoperative Cognitive Dysfunction—A Phase III Double Blind, Randomized Clinical Trial

PubMed Central

Pereira, Valeria Fontenelle Angelim; Pietrobon, Ricardo S.; Schmidt, Andre P.; Oses, Jean P.; Portela, Luis V.; Souza, Diogo O.; Vissoci, João Ricardo Nickenig; da Luz, Vinicius Fernando; Trintoni, Leticia Maria de Araujo de Souza; Nielsen, Karen C.; Carmona, Maria José Carvalho

2016-01-01

Postoperative cognitive dysfunction (POCD) is a multifactorial adverse event most frequently in elderly patients. This study evaluated the effect of dexamethasone on POCD incidence after noncardiac and nonneurologic surgery. METHODS: One hundred and forty patients (ASA I-II; age 60–87 years) took part in a prospective phase III, double blind, randomized study involving the administration or not of 8 mg of IV dexamethasone before general anesthesia under bispectral index (BIS) between 35–45 or 46–55. Neuropsychological tests were applied preoperatively and on the 3rd, 7th, 21st, 90th and 180th days after surgery and compared with normative data. S100β was evaluated before and 12 hours after induction of anesthesia. The generalized estimating equations (GEE) method was applied, followed by the posthoc Bonferroni test considering P<0.05 as significant. RESULTS: On the 3rd postoperative day, POCD was diagnosed in 25.2% and 15.3% of patients receiving dexamethasone, BIS 35–45, and BIS 46–55 groups, respectively. Meanwhile, POCD was present in 68.2% and 27.2% of patients without dexamethasone, BIS 35–45 and BIS 46–55 groups (p<0.0001). Neuropsychological tests showed that dexamethasone associated to BIS 46–55 decreased the incidence of POCD, especially memory and executive function. The administration of dexamethasone might have prevented the postoperative increase in S100β serum levels. CONCLUSION: Dexamethasone can reduce the incidence of POCD in elderly patients undergoing surgery, especially when associated with BIS 46–55. The effect of dexamethasone on S100β might be related with some degree of neuroprotection. Trial Registration: www.clinicaltrials.gov NCT01332812 PMID:27152422

The effects of inpatient exercise therapy on the length of hospital stay in stages I-III colon cancer patients: randomized controlled trial.

PubMed

Ahn, Ki-Yong; Hur, Hyuk; Kim, Dong-Hyun; Min, Jihee; Jeong, Duck Hyoun; Chu, Sang Hui; Lee, Ji Won; Ligibel, Jennifer A; Meyerhardt, Jeffrey A; Jones, Lee W; Jeon, Justin Y; Kim, Nam Kyu

2013-05-01

This study aimed to examine the effects of a postsurgical, inpatient exercise program on postoperative recovery in operable colon cancer patients We conducted the randomized controlled trial with two arms: postoperative exercise vs. usual care. Patients with stages I-III colon cancer who underwent colectomy between January and December 2011 from the Colorectal Cancer Clinic, were recruited for the study. Subjects in the intervention group participated in the postoperative inpatient exercise program consisted of twice daily exercise, including stretching, core, balance, and low-intensity resistance exercises. The usual care group was not prescribed a structured exercise program. The primary endpoint was the length of hospital stay. Secondary endpoints were time to flatus, time to first liquid diet, anthropometric measurements, and physical function measurements. A total of 31 (86.1 %) patients completed the trial, with adherence to exercise interventions at 84.5 %. The mean length of hospital stay was 7.82 ± 1.07 days in the exercise group compared with 9.86 ± 2.66 days in usual care (mean difference, 2.03 days; 95 % confidence interval (CI), -3.47 to -0.60 days; p = 0.005) in per-protocol analysis. The mean time to flatus was 52.18 ± 21.55 h in the exercise group compared with 71.86 ± 29.2 h in the usual care group (mean difference, 19.69 h; 95 % CI, -38.33 to -1.04 h; p = 0.036). Low-to-moderate-intensity postsurgical exercise reduces length of hospital stay and improves bowel motility after colectomy procedure in patients with stages I-III colon cancer.

Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

PubMed Central

Wolff, Antonio C.; Lazar, Ann A.; Bondarenko, Igor; Garin, August M.; Brincat, Stephen; Chow, Louis; Sun, Yan; Neskovic-Konstantinovic, Zora; Guimaraes, Rodrigo C.; Fumoleau, Pierre; Chan, Arlene; Hachemi, Soulef; Strahs, Andrew; Cincotta, Maria; Berkenblit, Anna; Krygowski, Mizue; Kang, Lih Lisa; Moore, Laurence; Hayes, Daniel F.

2013-01-01

Purpose Recent data showed improvement in progression-free survival (PFS) when adding everolimus to exemestane in patients with advanced breast cancer experiencing recurrence/progression after nonsteroidal aromatase inhibitor (AI) therapy. Here, we report clinical outcomes of combining the mammalian target of rapamycin (mTOR) inhibitor temsirolimus with letrozole in AI-naive patients. Patients and Methods This phase III randomized placebo-controlled study tested efficacy/safety of first-line oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) versus letrozole/placebo in 1,112 patients with AI-naive, hormone receptor–positive advanced disease. An independent data monitoring committee recommended study termination for futility at the second preplanned interim analysis (382 PFS events). Results Patients were balanced (median age, 63 years; 10% stage III, 40% had received adjuvant endocrine therapy). Those on letrozole/temsirolimus experienced more grade 3 to 4 events (37% v 24%). There was no overall improvement in primary end point PFS (median, 9 months; hazard ratio [HR], 0.90; 95% CI, 0.76 to 1.07; P = .25) nor in the 40% patient subset with prior adjuvant endocrine therapy. An exploratory analysis showed improved PFS favoring letrozole/temsirolimus in patients ≤ age 65 years (9.0 v 5.6 months; HR, 0.75; 95% CI, 0.60 to 0.93; P = .009), which was separately examined by an exploratory analysis of 5-month PFS using subpopulation treatment effect pattern plot methodology (P = .003). Conclusion Adding temsirolimus to letrozole did not improve PFS as first-line therapy in patients with AI-naive advanced breast cancer. Exploratory analyses of benefit in younger postmenopausal patients require external confirmation. PMID:23233719

Active transport on disordered microtubule networks: The generalized random velocity model

NASA Astrophysics Data System (ADS)

Kahana, Aviv; Kenan, Gilad; Feingold, Mario; Elbaum, Michael; Granek, Rony

2008-11-01

The motion of small cargo particles on microtubules by means of motor proteins in disordered microtubule networks is investigated theoretically using both analytical tools and computer simulations. Different network topologies in two and three dimensions are considered, one of which has been recently studied experimentally by Salman [Biophys. J. 89, 2134 (2005)]. A generalization of the random velocity model is used to derive the mean-square displacement of the cargo particle. We find that all cases belong to the class of anomalous superdiffusion, which is sensitive mainly to the dimensionality of the network and only marginally to its topology. Yet in three dimensions the motion is very close to simple diffusion, with sublogarithmic corrections that depend on the network topology. When details of the thermal diffusion in the bulk solution are included, no significant change to the asymptotic time behavior is found. However, a small asymmetry in the mean microtubule polarity affects the corresponding long-time behavior. We also study a three-dimensional model of the microtubule network in living animal cells. Three first-passage-time problems of intracellular transport are simulated and analyzed for different motor processivities: (i) cargo that originates near the nucleus and has to reach the membrane, (ii) cargo that originates from the membrane and has to reach the nucleus, and (iii) cargo that leaves the nucleus and has to reach a specific target in the cytoplasm. We conclude that while a higher motor processivity increases the transport efficiency in cases (i) and (ii), in case (iii) it has the opposite effect. We conjecture that the balance between the different network tasks, as manifested in cases (i) and (ii) versus case (iii), may be the reason for the evolutionary choice of a finite motor processivity.

A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients.

PubMed

Floege, Jürgen; Covic, Adrian C; Ketteler, Markus; Rastogi, Anjay; Chong, Edward M F; Gaillard, Sylvain; Lisk, Laura J; Sprague, Stuart M

2014-09-01

Efficacy of PA21 (sucroferric oxyhydroxide), a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder, was compared with that of sevelamer carbonate in an open-label, randomized, active-controlled phase III study. Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0-3.0 g per day and 348 received sevelamer 4.8-14.4 g per day for an 8-week dose titration, followed by 4 weeks without dose change, and then 12 weeks maintenance. Serum phosphorus reductions at week 12 were -0.71 mmol/l (PA21) and -0.79 mmol/l (sevelamer), demonstrating non-inferiority of, on average, three tablets of PA21 vs. eight of sevelamer. Efficacy was maintained to week 24. Non-adherence was 15.1% (PA21) vs. 21.3% (sevelamer). The percentage of patients that reported at least one treatment-emergent adverse event was 83.2% with PA21 and 76.1% with sevelamer. A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 (15.7%) vs. sevelamer (6.6%). Mild, transient diarrhea, discolored feces, and hyperphosphatemia were more frequent with PA21; nausea and constipation were more frequent with sevelamer. After 24 weeks, 99 hemodialysis patients on PA21 were re-randomized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose (250 mg per day (ineffective control)) in 49 patients. The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control. Thus, PA21 was effective in lowering serum phosphorus in dialysis patients, with similar efficacy to sevelamer carbonate, a lower pill burden, and better adherence.

Effect of UV irradiation on cutaneous cicatrices: a randomized, controlled trial with clinical, skin reflectance, histological, immunohistochemical and biochemical evaluations.

PubMed

Due, Eva; Rossen, Kristian; Sorensen, Lars Tue; Kliem, Anette; Karlsmark, Tonny; Haedersdal, Merete

2007-01-01

The aim of this study was to examine the effect of ultraviolet (UV) irradiation on human cutaneous cicatrices. In this randomized, controlled study, dermal punch biopsy wounds served as a wound healing model. Wounds healed by primary or second intention and were randomized to postoperative solar UV irradiation or to no UV exposure. Evaluations after 5 and 12 weeks included blinded clinical assessments, skin reflectance measurements, histology, immunohistochemistry, and biochemical analyses of the N-terminal propeptide from procollagen-1, hydroxyproline, hydroxylysine, and proline. Twelve weeks postoperatively, UV-irradiated cicatrices healing by second intention: (i) were significantly pointed out as the most disfiguring; (ii) obtained significantly higher scores of colour, infiltration and cicatrix area; and (iii) showed significantly higher increase in skin-reflectance measurements of skin-pigmentation vs. non-irradiated cicatrices. No histological, immunohistochemical or biochemical differences were found. In conclusion, postoperative UV exposure aggravates the clinical appearance of cicatrices in humans.

The Effects of the Bali Yoga Program for Breast Cancer Patients on Chemotherapy-Induced Nausea and Vomiting: Results of a Partially Randomized and Blinded Controlled Trial.

PubMed

Anestin, Annélie S; Dupuis, Gilles; Lanctôt, Dominique; Bali, Madan

2017-10-01

Complementary and alternative medicine has been shown to be beneficial in reducing chemotherapy-induced nausea and vomiting. However, conclusive results are lacking in order to confirm its usefulness. The purpose of this study was to determine whether a standardized yoga intervention could reduce these adverse symptoms. This was a partially randomized and blinded controlled trial comparing a standardized yoga intervention with standard care. Eligible patients were adults diagnosed with stages I to III breast cancer receiving chemotherapy. Patients randomized to the experimental group participated in an 8-week yoga program. There was no significant difference between the experimental and control groups on chemotherapy-induced nausea and vomiting after 8 weeks. Results suggest the yoga program is not beneficial in managing these adverse symptoms. However, considering preliminary evidence suggesting yoga's beneficial impact in cancer symptom management, methodological limitations should be explored and additional studies should be conducted.

Evaluation of the Efficacy of Tranexamic Acid on the Surgical Field in Primary Cleft Palate Surgery on Children-A Prospective, Randomized Clinical Study.

PubMed

Durga, Padmaja; Raavula, Parvathi; Gurajala, Indira; Gunnam, Poojita; Veerabathula, Prardhana; Reddy, Mukund; Upputuri, Omkar; Ramachandran, Gopinath

2015-09-01

To assess the effect of tranexamic acid on the quality of the surgical field. Prospective, randomized, double-blind study. Institutional, tertiary referral hospital. American Society of Anesthesiologists physical status class I patients, aged 8 to 60 months with Group II or III (Balakrishnan's classification) clefts scheduled for cleft palate repair. Children were randomized into two groups. The control group received saline, and the tranexamic acid group received tranexamic acid 10 mg/kg as a bolus, 15 minutes before incision. Grade of surgical field on a 10-point scale, surgeon satisfaction, and primary hemorrhage. Significant improvements were noted in surgeon satisfaction and median grade of assessment of the surgical field (4 [interquartile range, 4 to 6] in the control group vs. 3 [interquartile range, 2 to 4] in the test group; P = .003) in the tranexamic acid group compared to the control group. Preincision administration of 10 mg/kg of tranexamic acid significantly improved the surgical field during cleft palate repair.

Failures in Phase III: Causes and Consequences.

PubMed

Seruga, Bostjan; Ocana, Alberto; Amir, Eitan; Tannock, Ian F

2015-10-15

Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. ©2015 American Association for Cancer Research.

Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program.

PubMed

Barret, Juan P; Podmelle, Fred; Lipový, Břetislav; Rennekampff, Hans-Oliver; Schumann, Hauke; Schwieger-Briel, Agnes; Zahn, Tobias R; Metelmann, Hans-Robert

2017-09-01

The clinical significance of timely re-epithelialization is obvious in burn care, since delayed wound closure is enhancing the risk of wound site infection and extensive scarring. Topical treatments that accelerate wound healing are urgently needed to reduce these sequelae. Evidence from preliminary studies suggests that betulin can accelerate the healing of different types of wounds, including second degree burns and split-thickness skin graft wounds. The goal of this combined study program consisting of two randomized phase III clinical trials in parallel is to evaluate whether a topical betulin gel (TBG) is accelerating re-epithelialization of split-thickness skin graft (STSG) donor site wounds compared to standard of care. Two parallel blindly evaluated, randomised, controlled, multicentre phase III clinical trials were performed in adults undergoing STSG surgery (EudraCT nos. 2012-003390-26 and 2012-000777-23). Donor site wounds were split into two equal halves and randomized 1:1 to standard of care (a non-adhesive moist wound dressing) or standard of care plus TBG consisting of 10% birch bark extract and 90% sunflower oil (Episalvan, Birken AG, Niefern-Oeschelbronn, Germany). The primary efficacy assessment was the intra-individual difference in time to wound closure assessed from digital photographs by three blinded experts. A total of 219 patients were included and treated in the two trials. Wounds closed faster with TBG than without it (15.3 vs. 16.5 days; mean intra-individual difference=-1.1 days [95% CI, -1.5 to -0.7]; p<0.0001). This agreed with unblinded direct clinical assessment (difference=-2.1 days [95% CI, -2.7 to -1.5]; p<0.0001). Adverse events possibly related to treatment were mild or moderate and mostly at the application site. TBG accelerates re-epithelialization of partial thickness wounds compared to the current standard of care, providing a well-tolerated contribution to burn care in practice. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Randomized and controlled clinical study of modified prescriptions of Simiao Pill in the treatment of acute gouty arthritis.

PubMed

Shi, Xin-de; Li, Guo-chun; Qian, Zu-xi; Jin, Ze-qiu; Song, Yan

2008-03-01

To investigate the compatibility of a modified prescription of Simiao Pill in the treatment of acute gouty arthritis and to verify the clinical efficacy and safety of the drug through a clinical trial. A randomized and controlled clinical trial was designed based on clinical epidemiological principles. A total of 107 patients with acute gouty arthritis were enrolled and randomly assigned to four groups. The first group (Group I) included 27 patients taking gout prescription I; the second group (Group II) included 27 patients taking gout prescription II; the third group (Group III) included 28 patients taking gout prescription III; and the fourth group (control group) included 25 patients taking indomethacin and Benzobromarone as a control group. The duration of the treatment in all 4 groups was two weeks. After the treatment, the index of blood uric acid, blood leukocyte count, score of clinical symptoms, etc. were observed and measured. The total clinical effective rate of the three different modified prescriptions of the Simiao Pill was above 96%, significantly superior to that of the control group (68%, P<0.05). In terms of the improvement of main symptoms, the scores of four symptoms in all TCM treatment and control groups decreased after treatment, with statistically significant differences (P<0.05). Moreover, the scores markedly fell more so in the three Chinese herb groups than in the control group, and especially in Group III (P<0.05). There was a statistically significant difference in blood uric acid values before and after the treatment in the same group but no significant inter-group difference was seen. The modified prescriptions, based on the clinical research, clinical experience and traditional Chinese medicine theory, did show a better effect than Western medicine in this clinical study. Moreover, the prescriptions were precise, with the herbs inexpensive and readily available. The patients had good compliance with less adverse reactions noted. The modified prescription has a favorable prospect for future development and is worthy of further blind trials with larger samples.

Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial.

PubMed

Allegra, Carmen J; Yothers, Greg; O'Connell, Michael J; Beart, Robert W; Wozniak, Timothy F; Pitot, Henry C; Shields, Anthony F; Landry, Jerome C; Ryan, David P; Arora, Amit; Evans, Lisa S; Bahary, Nathan; Soori, Gamini; Eakle, Janice F; Robertson, John M; Moore, Dennis F; Mullane, Michael R; Marchello, Benjamin T; Ward, Patrick J; Sharif, Saima; Roh, Mark S; Wolmark, Norman

2015-11-01

National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A randomized, multicenter, phase II/III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG PC10-09.

PubMed

Lee, Ki Hyeong; Kim, Ji-Yeon; Lee, Moon Hee; Han, Hye Sook; Lim, Joo Han; Park, Keon Uk; Park, In Hae; Cho, Eun Kyung; Yoon, So Young; Kim, Jee Hyun; Choi, In Sil; Park, Jae Hoo; Choi, Young Jin; Kim, Hee-Jun; Jung, Kyung Hae; Kim, Si-Young; Oh, Do-Youn; Im, Seock-Ah

2016-04-01

Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with a high risk of myelosuppression. This phase II/III study was conducted to determine the adequate dose of pegteograstim, a new formulation of pegylated G-CSF, and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim. In the phase II part, 60 breast cancer patients who were undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy were randomly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle. The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients. The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1. The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar to that for the 6.0 mg pegteograstim (n = 26) (1.97 ± 1.79 days vs. 1.54 ± 0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the primary analysis revealed that the efficacy of pegteograstim (n = 56) was non-inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64 ± 1.18 days vs. 1.80 ± 1.05 days; difference, -0.15 ± 1.11 (p = 0.36, 97.5 % confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil count (ANC) recovery of pegteograstim (≥2000/μL) was significantly shorter than that of pegfilgrastim (8.85 ± 1.45 days vs. 9.83 ± 1.20 days, p < 0.0001). Other secondary endpoints showed no significant difference between the two groups. The safety profiles of the two groups did not differ significantly. Pegteograstim was shown to be as effective as pegfilgrastim in the reduction of chemotherapy-induced neutropenia in the breast cancer patients who were undergoing chemotherapy with a high risk of myelosuppression.

Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study.

PubMed

Akil, Bisher; Blick, Gary; Hagins, Debbie P; Ramgopal, Moti N; Richmond, Gary J; Samuel, Rafik M; Givens, Naomi; Vavro, Cindy; Song, Ivy H; Wynne, Brian; Ait-Khaled, Mounir

2015-01-01

The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG. VIKING-4 is a Phase III randomized, double-blind study in therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized to DTG 50 mg twice daily or placebo while continuing their failing regimen (without raltegravir or elvitegravir) for 7 days (clinicaltrials.gov identifier NCT01568892). At day 8, all subjects switched to open-label DTG 50 mg twice daily and optimized background therapy including ≥1 fully active drug. The primary end point was change from baseline in plasma HIV-1 RNA at day 8. The study population (n=30) was highly ART-experienced with advanced HIV disease. Patients had extensive baseline resistance to all approved antiretroviral classes. Adjusted mean change in HIV-1 RNA at day 8 was 
-1.06 log10 copies/ml for the DTG arm and 0.10 log10 copies/ml for the placebo arm (treatment difference -1.16 log10 copies/ml [-1.52, -0.80]; P<0.001). Overall, 47% and 57% of subjects had plasma HIV-1 RNA <50 and <400 copies/ml at week 24, and 40% and 53% at week 48, respectively. No discontinuations due to drug-related adverse events occurred in the study. The observed day 8 antiviral activity in this highly treatment-experienced population with INI-resistant HIV-1 was attributable to DTG. Longer-term efficacy (after considering baseline ART resistance) and safety during the open-label phase were in-line with the results of the larger VIKING-3 study.

Community-based Randomized Controlled Trial of Non-pharmacological Interventions in Prevention and Control of Hypertension among Young Adults.

PubMed

Saptharishi, Lg; Soudarssanane, Mb; Thiruselvakumar, D; Navasakthi, D; Mathanraj, S; Karthigeyan, M; Sahai, A

2009-10-01

Hypertension is a major chronic lifestyle disease. Several non-pharmacological interventions are effective in bringing down the blood pressure (BP). This study focuses on the effectiveness of such interventions among young adults. To measure the efficacy of physical exercise, reduction in salt intake, and yoga, in lowering BP among young (20-25) pre-hypertensives and hypertensives, and to compare their relative efficacies. The study was done in the urban service area of JIPMER. Pre-hypertensives and hypertensives, identified from previous studies, constituted the universe. The participants were randomized into one control and three interventional groups. A total of 113 subjects: 30, 28, 28 and 27 in four groups respectively participated for eight weeks: control (I), physical exercise (II) - brisk walking for 50-60 minutes, four days/week, salt intake reduction (III) - to at least half of their previous intake, and practice of yoga (IV) - for 30-45 minutes/day on at least five days/week. Efficacy was assessed using paired t test and ANOVA with Games Howell post hoc test. An intention to treat analysis was also performed. A total of 102 participants (29, 27, 25 and 21 in groups I, II, III and IV) completed the study. All three intervention groups showed a significant reduction in BP (SBP/DBP: 5.3/6.0 in group II, 2.6/3.7 in III, and 2.0/2.6 mm Hg in IV respectively). There was no significant change (SBP/DBP: 0.2/0.5 mmHg) of BP in control group (I). Physical exercise was most effective (considered individually); salt intake reduction and yoga were also effective. Physical exercise, salt intake reduction, and yoga are effective non-pharmacological interventions in significantly reducing BP among young hypertensives and pre-hypertensives. These can therefore be positively recommended for hypertensives. There is also a case to deploy these interventions in the general population.

A topical aqueous oxygen emulsion stimulates granulation tissue formation in a porcine second-degree burn wound.

PubMed

Li, Jie; Zhang, Yan-Ping; Zarei, Mina; Zhu, Linjian; Sierra, Jose Ollague; Mertz, Patricia M; Davis, Stephen C

2015-08-01

Oxygen is an essential substance for wound healing. Limited studies have shown that topical oxygen can influence healing. This study evaluated the effects of a Topical Oxygen Emulsion (TOE) on burn wound healing. A porcine second-degree burn wound model was used in the study. Burn wounds were randomly assigned to TOE, vehicle control, and no-treatment (air) groups. Effects of TOE on the granulation tissue formation and angiogenesis were studied using hematoxylin and eosin histological analysis. Protein production and gene expression of types I and III collagen and vascular endothelial growth factor (VEGF) were determined using immunofluorescent staining and Reverse Transcription and Polymerase Chain Reaction (RT-PCR), respectively. The TOE treated wounds exhibited better angiogenesis and granulation tissue formation by histology examination. The immunofluorescence staining and RT-PCR analysis demonstrated that protein production and mRNA expression of VEGF and collagen III were significantly higher in TOE treatment group than vehicle alone and air control groups, while there was no significant difference in the level of collagen I. Our data demonstrate that TOE enhances burn wound healing via stimulating the expression of VEGF and type III collagen and strongly indicates the potential use of TOE in wounds. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicenter, randomized, cross-over phase III trial of the 'Arbeitsgemeinschaft Internistische Onkologie'.

PubMed

Boeck, Stefan; Vehling-Kaiser, Ursula; Waldschmidt, Dirk; Kettner, Erika; Märten, Angela; Winkelmann, Cornelia; Klein, Stefan; Kojouharoff, Georgi; Gauler, Thomas; Fischer von Weikersthal, Ludwig; Clemens, Michael R; Geissler, Michael; Greten, Tim F; Hegewisch-Becker, Susanna; Neugebauer, Sascha; Heinemann, Volker

2010-01-01

To date, only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment-naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14 days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of treatment failure, patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was the time to treatment failure of second-line therapy (TTF2). This interim analysis of toxicity contains safety data from the first 127 randomized patients. During first-line therapy, patients received a median number of three treatment cycles (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27% of treatment cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of all cycles. Grade 3/4 hematological toxicity was <10% in both the arms; major grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs. 12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed. In conclusion, this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.

In vitro remineralization of enamel subsurface lesions and assessment of dentine tubule occlusion from NaF dentifrices with and without calcium.

PubMed

Prabhakar, A R; Manojkumar, A Jaiswal; Basappa, N

2013-01-01

Currently, fluoride is the most effective preventive treatment for remineralization of incipient carious lesions and dentinal hypersensitivity due to wasting disorders. The products containing fluoride, calcium and phosphate are also claim to remineralize early, non-cavitated enamel demineralization. The aim of this study was to investigate and compare the efficacy of two such products, Tooth Mousse and Clinpro tooth crème on remineralization and tubule occluding ability with 5000ppm fluoride-containing toothpaste. Thirty third molar teeth were placed in demineralizing solution for 5 days such that only a window of 1mm x 5mm was exposed to the environment to produce artificial caries-like lesions and randomly assigned to three groups: Group I, 5000ppm sodium fluoride; Group II, GC MI paste plus and Group III, Clinpro tooth crème. Axial longitudinal sections of 140-160 μm of each tooth which included the artificial carious lesion taken and were photographed under polarized light microscope. The demineralized areas were then quantified with a computerized imaging system. The experimental materials were applied onto the tooth sections as a topical coating and subjected to pH-cycling for 28 days. To evaluate tubule occlusion ability, thirty dentin specimens of 2mm thickness were obtained from cervical third of sound third molars. Specimens were ultrasonicated and etched with 6% citric acid for 2 minutes to simulate the hypersensitive dentin. Specimens were randomly divided into above mentioned three groups (n=10). The test agents were brushed over the specimens with an electric toothbrush, prepared and observed under Scanning Electron Microscope for calculation of the percentage of occluded tubules. Group I showed a significantly greater percentage of remineralization than Group III and Group II. Comparison of the remineralization potential between group II and group III were not significant.In case of dentine hypersensitivity, Group I and group III showed greater percentage of tubule occlusion ability than Group II. Intergroup comparison of the tubule occlusion potential of group I and group III were not significant. Within the limitations of our study, sodium fluoride showed relatively greatest remineralizing and dentinal tubule occlusion property when compared with GC MI paste plus and Clinpro tooth crème.

50 CFR 660.15 - Equipment requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... water, slime, mud, debris, or other materials. Scale printouts must show: (A) The vessel name and...; (ii) Random Access Memory (RAM): 256 megabytes (MB) or higher; (iii) Hard disk space: (A) If already...

Adding Targeted Therapy to Treatment for Esophageal Cancer

Cancer.gov

In this phase III clinical trial, people with confirmed HER2-positive locally advanced esophageal cancer will be randomly assigned to receive preoperative radiation therapy and chemotherapy, with or without trastuzumab.

50 CFR 660.15 - Equipment requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... water, slime, mud, debris, or other materials. Scale printouts must show: (A) The vessel name and...; (ii) Random Access Memory (RAM): 256 megabytes (MB) or higher; (iii) Hard disk space: (A) If already...

50 CFR 660.15 - Equipment requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... water, slime, mud, debris, or other materials. Scale printouts must show: (A) The vessel name and...; (ii) Random Access Memory (RAM): 256 megabytes (MB) or higher; (iii) Hard disk space: (A) If already...

Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

PubMed

Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

2018-05-01

The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

PubMed

Choi, Yoon Jin; Lee, Dong Ho; Choi, Myung Gyu; Lee, Sung Joon; Kim, Sung Kook; Song, Geun Am; Rhee, Poong Lyul; Jung, Hwoon Yong; Kang, Dae Hwan; Lee, Yong Chan; Lee, Si Hyung; Choi, Suck Chei; Shim, Ki Nam; Seol, Sang Yong; Moon, Jeong Seop; Shin, Yong Woon; Kim, Hyun Soo; Lee, Soo Teik; Cho, Jin Woong; Choi, Eun Kwang; Lee, Oh Young; Jang, Jin Seok

2017-11-01

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670). © 2017 The Korean Academy of Medical Sciences.

Effect of Daikenchuto (TJ-100) on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: study protocol for a randomized controlled trial.

PubMed

Hoshino, Nobuaki; Kawada, Kenji; Hida, Koya; Wada, Toshiaki; Takahashi, Ryo; Yoshitomi, Mami; Sakai, Yoshiharu

2017-11-21

Postoperative paralytic ileus can be a difficult complication for both surgeons and patients. Causes and treatments have been discussed for more than two centuries, but have not yet been fully resolved. Daikenchuto (TJ-100, DKT) is a traditional Japanese herbal medicine. Recently, some beneficial mechanisms of DKT to relieve paralytic ileus have been reported. DKT can suppress inflammation, increase intestinal blood flow, and accelerate bowel movements. Therefore, we have designed a randomized controlled trial to investigate the effects of DKT on postoperative gastrointestinal symptoms following laparoscopic colectomy in patients with left-sided colon cancer at a single institution. As primary endpoints, the following outcomes will be evaluated: (i) grade of abdominal pain determined using the numeric rating scale (NRS), (ii) grade of abdominal distention determined using the NRS, and (iii) quality of life determined using the Gastrointestinal Quality Life Index (GIQLI). As secondary endpoints, the following will be evaluated: (i) postoperative nutritional status (Onodera's Prognostic Nutritional Index (PNI) and the Controlling Nutritional Status score (CONUT score)), (ii) duration to initial flatus, (iii) duration to initial defecation, (iv) bowel gas volume, (v) character of stool (Bristol Stool Form Scale), (vi) defecation frequency per day, (vii) postoperative complications (Clavien-Dindo classification), (viii) length of postoperative hospital stay, and (ix) metabolites in the stool and blood. This trial is an open-label study, and needs to include 40 patients (20 patients per group) and is expected to span 2 years. To our knowledge, this is the first randomized controlled trial to investigate the effects of DKT on postoperative subjective outcomes (i.e., postoperative quality of life) following laparoscopic colectomy as primary endpoints. Exploratory metabolomics analysis of metabolites in stool and blood will be conducted in this trial, which previously has only been performed in a few human studies. The study aims to guide a future full-scale pragmatic randomized trial to assess the overall effectiveness of DKT to improve the postoperative quality of life following laparoscopic colectomy. UMIN-CTR (Japan), UMIN000023318 . Registered on 25 July 2016.

Surrogate endpoints in randomized cardiovascular clinical trials.

PubMed

Domanski, Michael; Pocock, Stuart; Bernaud, Corine; Borer, Jeffrey; Geller, Nancy; Revkin, James; Zannad, Faiez

2011-08-01

Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclusion regarding treatment effect on a CEI requires prior rigorous validation of the surrogate. Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Lubiprostone: in constipation-predominant irritable bowel syndrome.

PubMed

Carter, Natalie J; Scott, Lesley J

2009-06-18

Lubiprostone is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of human gastrointestinal epithelial cells, thereby increasing chloride-rich fluid secretion. Although the mechanism is unclear, this may then decrease intestinal transit time, allowing the passage of stool and alleviating symptoms of constipation. Oral lubiprostone was effective in the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C) in large (n = 193-583) phase II (dose-finding) and phase III randomized, double-blind, placebo-controlled, multicentre trials. The number of patients with IBS-C demonstrating an overall response to treatment (primary endpoint) in the two phase III trials was significantly greater in patients receiving lubiprostone 8 microg twice daily for 3 months than in those receiving placebo. In addition, a randomized, 4-week withdrawal period at the end of one of the phase III trials demonstrated that discontinuation of lubiprostone was not associated with rebound of IBS symptoms. Lubiprostone was generally well tolerated in clinical trials, with the majority of adverse events being of mild to moderate severity. In patients with IBS-C who received lubiprostone 8 microg twice daily, nausea was the most frequently occurring adverse event that was considered possibly or probably treatment related. No serious treatment-related adverse events were reported in a 36-week open-label extension to the phase III trials.

Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

PubMed

Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

2009-06-01

Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years apart, and subject to evolving analytic plans influenced by new data that emerge over time.

Modified Angle's Classification for Primary Dentition

PubMed Central

Chandranee, Kaushik Narendra; Chandranee, Narendra Jayantilal; Nagpal, Devendra; Lamba, Gagandeep; Choudhari, Purva; Hotwani, Kavita

2017-01-01

Aim: This study aims to propose a modification of Angle's classification for primary dentition and to assess its applicability in children from Central India, Nagpur. Methods: Modification in Angle's classification has been proposed for application in primary dentition. Small roman numbers i/ii/iii are used for primary dentition notation to represent Angle's Class I/II/III molar relationships as in permanent dentition, respectively. To assess applicability of modified Angle's classification a cross-sectional preschool 2000 children population from central India; 3–6 years of age residing in Nagpur metropolitan city of Maharashtra state were selected randomly as per the inclusion and exclusion criteria. Results: Majority 93.35% children were found to have bilateral Class i followed by 2.5% bilateral Class ii and 0.2% bilateral half cusp Class iii molar relationships as per the modified Angle's classification for primary dentition. About 3.75% children had various combinations of Class ii relationships and 0.2% children were having Class iii subdivision relationship. Conclusions: Modification of Angle's classification for application in primary dentition has been proposed. A cross-sectional investigation using new classification revealed various 6.25% Class ii and 0.4% Class iii molar relationships cases in preschool children population in a metropolitan city of Nagpur. Application of the modified Angle's classification to other population groups is warranted to validate its routine application in clinical pediatric dentistry. PMID:29326514

Association of Psoriasis and Metabolic Syndrome in Latin America: A Systematic Review and Meta-Analysis.

PubMed

Rodríguez-Zúñiga, M J M; Cortez-Franco, F; Quijano-Gomero, E

2017-05-01

Meta-analyses have found evidence of a relationship between psoriasis and metabolic syndrome, but Latin American populations have not been included. We performed a systematic review and meta-analysis of observational studies including adults with psoriasis and metabolic syndrome indexed in Medline, Scopus, SciELO, Google Scholar, Science Direct, and LILACS between 1980 and 2016. We computed pooled odds ratios (OR) with a random effects model and analyzed subgroups according to patient variables used in the studies. Five studies with a total of 241 patients with psoriasis were found; 46.5% of the patients also had metabolic syndrome (pooled OR, 2.63; 95% CI: 1.11-6.23; P=.03). In studies using the Adult Treatment Panel III (ATP-III) criteria for metabolic syndrome, the pooled OR was similar at 3.97 (95% CI: 1.27-21.42). Studies that included patients with chronic and severe disease detected higher risk for metabolic syndrome (pooled OR, 6.65; 95% CI: 3.32-13.31). Limitations are that few studies have been done in Latin America, heterogeneity was high, and inconsistency was found across studies. The association between psoriasis and metabolic syndrome is high in Latin America. The association is stronger when psoriasis is chronic and severe and when the ATP-III criteria are used for diagnosis. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Integrating Comparative Effectiveness Design Elements and Endpoints Into a Phase III, Randomized Clinical Trial (SWOG S1007) Evaluating OncotypeDX-Guided Management for Women With Breast Cancer Involving Lymph Nodes

PubMed Central

Ramsey, Scott D.; Barlow, William E.; Gonzalez-Angulo, Ana M.; Tunis, Sean; Baker, Laurence; Crowley, John; Deverka, Patricia; Veenstra, David; Hortobagyi, Gabriel N.

2012-01-01

Women with breast cancer involving the lymph nodes are typically treated with cytotoxic chemotherapy. Retrospective evaluations of prior studies suggest that the 21-gene test (OncotypeDX®), may allow identification of those who can safely avoid chemotherapy. To better understand the performance of the 21-gene test, the RxPONDER (Rx for Positive Node, Endocrine Responsive breast cancer) study was designed, a multicenter Phase III trial randomizing women with hormone receptor-positive and HER2-negative breast cancer involving 1–3 lymph nodes and a 21-gene assay recurrence score (RS) of 25 or less to endocrine therapy alone versus chemotherapy followed by endocrine therapy. As one of the first large-scale comparative-effectiveness studies in oncology, RxPONDER utilized an external stakeholder group to help inform the design of the trial. Stakeholders met with representatives of SWOG over several months through a structured discussion process. The stakeholder engagement process resulted in several changes being made to the trial design. In addition, stakeholder representatives from the health insurance industry provided guidance regarding a mechanism whereby the costs of OncotypeDX® would be paid by the majority of health insurers as part of the trial. The process may serve as a template for future studies evaluating the comparative effectiveness of genomic tests in oncology, particularly those that are conducted within cooperative clinical trials groups. PMID:23000081

Seven lessons from manyfield inflation in random potentials

NASA Astrophysics Data System (ADS)

Dias, Mafalda; Frazer, Jonathan; Marsh, M. C. David

2018-01-01

We study inflation in models with many interacting fields subject to randomly generated scalar potentials. We use methods from non-equilibrium random matrix theory to construct the potentials and an adaption of the `transport method' to evolve the two-point correlators during inflation. This construction allows, for the first time, for an explicit study of models with up to 100 interacting fields supporting a period of `approximately saddle-point' inflation. We determine the statistical predictions for observables by generating over 30,000 models with 2–100 fields supporting at least 60 efolds of inflation. These studies lead us to seven lessons: i) Manyfield inflation is not single-field inflation, ii) The larger the number of fields, the simpler and sharper the predictions, iii) Planck compatibility is not rare, but future experiments may rule out this class of models, iv) The smoother the potentials, the sharper the predictions, v) Hyperparameters can transition from stiff to sloppy, vi) Despite tachyons, isocurvature can decay, vii) Eigenvalue repulsion drives the predictions. We conclude that many of the `generic predictions' of single-field inflation can be emergent features of complex inflation models.

Outcomes of gait trainer use in home and school settings for children with motor impairments: a systematic review.

PubMed

Paleg, Ginny; Livingstone, Roslyn

2015-11-01

To summarize and critically appraise evidence regarding use of gait trainers (walkers providing trunk and pelvic support) at home or school with children who are unable to walk independently or with hand-held walkers. Searches were performed in seven electronic databases including EBM Reviews, CINAHL, Medline and EMBASE for publications in English from database inception to November 2014. Included studies involved at least one child with a mobility limitation and measured an outcome related to gait trainer use. Articles were appraised using American Academy of Cerebral Palsy and Developmental Medicine criteria for group and single-subject designs and quality ratings completed for studies rated levels I-III. The PRISMA statement was followed with inclusion criteria set a priori. Two reviewers independently screened titles, abstracts and full-text articles. Seventeen studies involving 182 children were included. Evidence from one small randomized controlled trial suggests a non-significant trend toward increased walking distance while the other evidence level II study (concurrent multiple baseline design) reports increased number of steps. Two level III studies (non-randomized two-group studies) report statistically significant impact on mobility level with one finding significant impact on bowel function and an association between increased intervention time and bone mineral density. Remaining descriptive level evidence provides support for positive impact on a range of activity outcomes, with some studies reporting impact on affect, motivation and participation with others. Evidence supporting outcomes for children using gait trainers is primarily descriptive and, while mainly positive, is insufficient to draw firm conclusions. © The Author(s) 2015.

A mixed methods protocol for developing and testing implementation strategies for evidence-based obesity prevention in childcare: a cluster randomized hybrid type III trial.

PubMed

Swindle, Taren; Johnson, Susan L; Whiteside-Mansell, Leanne; Curran, Geoffrey M

2017-07-18

Despite the potential to reach at-risk children in childcare, there is a significant gap between current practices and evidence-based obesity prevention in this setting. There are few investigations of the impact of implementation strategies on the uptake of evidence-based practices (EBPs) for obesity prevention and nutrition promotion. This study protocol describes a three-phase approach to developing and testing implementation strategies to support uptake of EBPs for obesity prevention practices in childcare (i.e., key components of the WISE intervention). Informed by the i-PARIHS framework, we will use a stakeholder-driven evidence-based quality improvement (EBQI) process to apply information gathered in qualitative interviews on barriers and facilitators to practice to inform the design of implementation strategies. Then, a Hybrid Type III cluster randomized trial will compare a basic implementation strategy (i.e., intervention as usual) with an enhanced implementation strategy informed by stakeholders. All Head Start centers (N = 12) within one agency in an urban area in a southern state in the USA will be randomized to receive the basic or enhanced implementation with approximately 20 classrooms per group (40 educators, 400 children per group). The educators involved in the study, the data collectors, and the biostastician will be blinded to the study condition. The basic and enhanced implementation strategies will be compared on outcomes specified by the RE-AIM model (e.g., Reach to families, Effectiveness of impact on child diet and health indicators, Adoption commitment of agency, Implementation fidelity and acceptability, and Maintenance after 6 months). Principles of formative evaluation will be used throughout the hybrid trial. This study will test a stakeholder-driven approach to improve implementation, fidelity, and maintenance of EBPs for obesity prevention in childcare. Further, this study provides an example of a systematic process to develop and test a tailored, enhanced implementation strategy. ClinicalTrials.gov, NCT03075085.

Phase III Trial of Ipilimumab Combined With Paclitaxel and Carboplatin in Advanced Squamous Non-Small-Cell Lung Cancer.

PubMed

Govindan, Ramaswamy; Szczesna, Aleksandra; Ahn, Myung-Ju; Schneider, Claus-Peter; Gonzalez Mella, Pablo Fernando; Barlesi, Fabrice; Han, Baohui; Ganea, Doina Elena; Von Pawel, Joachim; Vladimirov, Vladimir; Fadeeva, Natalia; Lee, Ki Hyeong; Kurata, Takayasu; Zhang, Li; Tamura, Tomohide; Postmus, Pieter E; Jassem, Jacek; O'Byrne, Kenneth; Kopit, Justin; Li, Mingshun; Tschaika, Marina; Reck, Martin

2017-10-20

Purpose Patients with squamous non-small-cell lung cancer (NSCLC) have poor prognosis and limited treatment options. This randomized, double-blind, phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC. Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were randomly assigned (1:1) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles, with ipilimumab or placebo from cycles 3 to 6 and then, after induction treatment, ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better. The primary end point was overall survival (OS) in patients receiving at least one dose of blinded study therapy. Results Of 956 randomly assigned patients, 749 received at least one dose of blinded study therapy (chemotherapy plus ipilimumab, n = 388; chemotherapy plus placebo, n = 361). Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo (hazard ratio, 0.91; 95% CI, 0.77 to 1.07; P = .25). Median progression-free survival was 5.6 months for both groups (hazard ratio, 0.87; 95% CI, 0.75 to 1.01). Rates of grade 3 or 4 treatment-related adverse events (TRAEs), any-grade serious TRAEs, and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab (51%, 33%, and 28%, respectively) than with chemotherapy plus placebo (35%, 10%, and 7%, respectively). Seven treatment-related deaths occurred with chemotherapy plus ipilimumab, and one occurred with chemotherapy plus placebo. Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC. The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies. Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population.

Study Design and Rationale for a Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Selumetinib in Combination With Docetaxel as Second-Line Treatment in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer (SELECT-1).

PubMed

Jänne, Pasi A; Mann, Helen; Ghiorghiu, Dana

2016-03-01

Oncogenic KRAS mutations represent the largest genomically defined subset of lung cancer, and are associated with activation of the RAS/RAF/MEK/ERK pathway. There are currently no therapies specifically approved for patients with KRAS-mutant (KRASm) non-small-cell lung cancer (NSCLC), and these patients derive less clinical benefit from chemotherapy than the overall NSCLC population. In a recent phase II study, selumetinib (AZD6244, ARRY-142886), an oral, potent and selective, allosteric MEK1/2 inhibitor with a short half-life, combined with docetaxel, improved clinical outcome as second-line treatment for patients with KRASm NSCLC. This combination will be further evaluated in the phase III SELECT-1 study. SELECT-1 (NCT01933932) is a randomized, double-blind, placebo-controlled phase III study assessing the efficacy and safety of selumetinib plus docetaxel in patients with KRASm locally advanced or metastatic NSCLC, eligible for second-line treatment. The primary endpoint is progression-free survival (PFS); secondary endpoints include overall survival, objective response rate, duration of response, and safety and tolerability. Approximately 634 patients will be randomized 1:1 to receive selumetinib (75 mg twice daily on a continuous oral administration schedule) in combination with docetaxel (75 mg/m(2), intravenously on day 1 of every 21-day cycle) or placebo in combination with docetaxel (same schedule), until objective disease progression. Patients may continue to receive treatment after objective disease progression if deemed appropriate by the investigator. If the primary endpoint of PFS is met, selumetinib plus docetaxel would be the first targeted treatment for patients with KRASm advanced NSCLC who are eligible for second-line treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial).

PubMed

Kröger, Nicolaus; Iacobelli, Simona; Franke, Georg-Nikolaus; Platzbecker, Uwe; Uddin, Ruzena; Hübel, Kai; Scheid, Christof; Weber, Thomas; Robin, Marie; Stelljes, Matthias; Afanasyev, Boris; Heim, Dominik; Deliliers, Giorgio Lambertenghi; Onida, Francesco; Dreger, Peter; Pini, Massimo; Guidi, Stefano; Volin, Liisa; Günther, Andreas; Bethge, Wolfgang; Poiré, Xavier; Kobbe, Guido; van Os, Marleen; Brand, Ronald; de Witte, Theo

2017-07-01

Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.

Three-Drug Combination for Relapsed Multiple Myeloma

Cancer.gov

A summary of Interim results from an international, randomized phase III trial that suggest that adding carfilzomib (Kyprolis®) to a standard treatment improves outcomes for patients with multiple myeloma whose cancer has relapsed.

Denosumab Effective for Multiple Myeloma and Solid Tumors

Cancer.gov

Results from a randomized phase III trial of denosumab to prevent skeletal related events in several types of cancer were published online February 22, 2011, in the Journal of Clinical Oncology (JCO).

Nivolumab-Based Treatments for Advanced Melanoma

Cancer.gov

A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study.

PubMed

Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Ito, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong

2017-09-01

The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600pg/mL, or NT-proBNP ≥400pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100mg bid or enalapril 5mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200mg bid or enalapril 10mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biowaiver extension potential to BCS Class III high solubility-low permeability drugs: bridging evidence for metformin immediate-release tablet.

PubMed

Cheng, Ching-Ling; Yu, Lawrence X; Lee, Hwei-Ling; Yang, Chyun-Yu; Lue, Chang-Sha; Chou, Chen-Hsi

2004-07-01

The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC0-t, AUC0-infinity) and maximal concentration (Cmax). The 90% confidence intervals for the ratio of means were found within the acceptance range of 80-125% for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs.

A randomized controlled Phase III trial comparing 2-weekly docetaxel combined with cisplatin plus fluorouracil (2-weekly DCF) with cisplatin plus fluorouracil (CF) in patients with metastatic or recurrent esophageal cancer: rationale, design and methods of Japan Clinical Oncology Group study JCOG1314 (MIRACLE study).

PubMed

Kataoka, Kozo; Tsushima, Takahiro; Mizusawa, Junki; Hironaka, Shuichi; Tsubosa, Yasuhiro; Kii, Takayuki; Shibuya, Yuichi; Chin, Keisho; Katayama, Hiroshi; Kato, Ken; Fukuda, Haruhiko; Kitagawa, Yuko

2015-05-01

Chemotherapy with cisplatin plus fluorouracil is the current standard treatment for metastatic or recurrent esophageal cancer. We have developed a 2-weekly docetaxel combined with CF regimen and conducted a Phase I/II trial for metastatic or recurrent esophageal cancer (JCOG0807). Promising efficacy and safety were shown in JCOG0807, and we have commenced a Phase III trial in September 2014 to confirm the superiority of 2-weekly DCF to CF for patients with metastatic or recurrent esophageal cancer. A total of 240 patients will be accrued from 41 Japanese institutions over a period of 4 years. The primary end point is overall survival. The secondary end points are progression-free survival, response rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015107 (http://www.umin.ac.jp/ctr/index.htm). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Rotigotine transdermal system and evaluation of pain in patients with Parkinson's disease: a post hoc analysis of the RECOVER study.

PubMed

Kassubek, Jan; Chaudhuri, Kallol Ray; Zesiewicz, Theresa; Surmann, Erwin; Boroojerdi, Babak; Moran, Kimberly; Ghys, Liesbet; Trenkwalder, Claudia

2014-03-06

Pain is a troublesome non-motor symptom of Parkinson's disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system. Improvements were also reported on a Likert pain scale (measuring any type of pain). This post hoc analysis of RECOVER further evaluates the effect of rotigotine on pain, and whether improvements in pain may be attributable to benefits in motor function or sleep disturbance. PD patients with unsatisfactory early-morning motor impairment were randomized to optimal-dose (up to 16 mg/24 h) rotigotine or placebo, maintained for 4 weeks. Pain was assessed in the early-morning using an 11-point Likert pain scale (rated average severity of pain (of any type) over the preceding 12 hours from 0 [no pain] to 10 [worst pain ever experienced]). Post hoc analyses for patients reporting 'any' pain (pain score ≥1) at baseline, and subgroups reporting 'mild' (score 1-3), and 'moderate-to-severe' pain (score ≥4) were performed. Likert pain scale change from baseline in rotigotine-treated patients was further analyzed based on a UPDRS III/PDSS-2 responder analysis (a responder defined as showing a ≥30% reduction in early morning UPDRS III total score or PDSS-2 total score). As post hoc analyses, all p values presented are exploratory. Of 267 patients with Likert pain data (178 rotigotine, 89 placebo), 187 (70%) reported 'any' pain; of these 87 (33%) reported 'mild', and 100 (37%) 'moderate-to-severe' pain. Change from baseline pain scores decreased with rotigotine compared with placebo in patients with 'any' pain (-0.88 [95% CI: -1.56, -0.19], p = 0.013), and in the subgroup with 'moderate-to-severe' pain (-1.38 [-2.44, -0.31], p = 0.012). UPDRS III or PDSS-2 responders showed greater improvement in pain than non-responders. The results from this post hoc analysis of the RECOVER study suggest that pain was improved in patients with PD treated with rotigotine; this may be partly attributable to benefits in motor function and sleep disturbances. Prospective studies are warranted to investigate this potential benefit and the clinical relevance of these findings.

Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study.

PubMed

Pepin, Stephanie; Szymanski, Henryk; Rochín Kobashi, Ilya Angélica; Villagomez Martinez, Sandra; González Zamora, José Francisco; Brzostek, Jerzy; Huang, Li-Min; Chiu, Cheng-Hsun; Chen, Po-Yen; Ahonen, Anitta; Forstén, Aino; Seppä, Ilkka; Quiroz, René Farfán; Korhonen, Tiina; Rivas, Enrique; Monfredo, Celine; Hutagalung, Yanee; Menezes, Josemund; Vesikari, Timo

2016-12-01

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3-8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

Comparison between group and personal rehabilitation for dementia in a geriatric health service facility: single-blinded randomized controlled study.

PubMed

Tanaka, Shigeya; Honda, Shin; Nakano, Hajime; Sato, Yuko; Araya, Kazufumi; Yamaguchi, Haruyasu

2017-05-01

The aim of this study was to compare the effects of rehabilitation involving group and personal sessions on demented participants. This single-blinded randomized controlled trial included 60 elderly participants with dementia in a geriatric health service facility, or R oken. Staff members, who did not participate in the intervention, examined cognitive function, mood, communication ability, severity of dementia, objective quality of life, vitality, and daily behaviour. After a baseline assessment, participants were randomly divided into three groups: (i) group intervention; (ii) personal intervention; and (iii) control. The 1-h group intervention (3-5 subjects) and 20-min personal intervention (one staff member per participant) were performed twice a week for 12 weeks (24 total sessions). The cognitive rehabilitation programme consisted of reminiscence, reality orientation, and physical exercise, and it was based on five principles of brain-activating rehabilitation; (i) pleasant atmosphere; (ii) communication; (iii) social roles; (iv) praising; and (v) errorless support. Data were analyzed after the second assessment. Outcome measures were analyzed in 43 participants-14 in the control group, 13 in group intervention, and 16 in personal intervention. Repeated measure ancova showed a significant interaction for cognitive function score (Mini-Mental State Examination) between group intervention and controls ( F  = 5.535, P = 0.029). In the post-hoc analysis, group intervention showed significant improvement (P = 0.016). Global severity of dementia tended to improve (P = 0.094) in group intervention compared to control (Mann-Whitney U -test). There were no significant interactions or improvements for other measurements. Group rehabilitation for dementia is more effective for improving cognitive function and global severity of dementia than personal rehabilitation in Roken. © 2016 Japanese Psychogeriatric Society.

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial.

PubMed

Kyriakopoulos, Christos E; Chen, Yu-Hui; Carducci, Michael A; Liu, Glenn; Jarrard, David F; Hahn, Noah M; Shevrin, Daniel H; Dreicer, Robert; Hussain, Maha; Eisenberger, Mario; Kohli, Manish; Plimack, Elizabeth R; Vogelzang, Nicholas J; Picus, Joel; Cooney, Matthew M; Garcia, Jorge A; DiPaola, Robert S; Sweeney, Christopher J

2018-04-10

Purpose Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume. Patients and Methods In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/m 2 for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional analyses of the prospectively defined low- and high-volume disease subgroups were performed. High-volume disease was defined as presence of visceral metastases and/or ≥ four bone metastases with at least one outside of the vertebral column and pelvis. Results At a median follow-up of 53.7 months, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59 to 0.89; P = .0018). For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50 to 0.79; P < .001). For those with low-volume disease (n = 277), no OS benefit was observed (HR, 1.04; 95% CI, 0.70 to 1.55; P = .86). Conclusion The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials.

PubMed

Lebwohl, Mark; Dinehart, Scott; Whiting, David; Lee, Peter K; Tawfik, Naji; Jorizzo, Joseph; Lee, James H; Fox, Terry L

2004-05-01

The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers. Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp. A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit. The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated. Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

PubMed

Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo

2016-10-01

We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

[Corifollitropin alfa in women stimulated for the first time in in vitro fertilization programme].

PubMed

Vraná-Mardešićová, N; Vobořil, J; Melicharová, L; Jelínková, L; Vilímová, Š; Mardešić, T

2017-01-01

To compare results after stimulation with corifollitropin alfa (Elonva) in unselected group of women entering for the first time in in vitro fertilization programme (IVF) with results from Phase III randomized trials with selected groups of women. Prospective study. Sanatorium Pronatal, Praha. 40 unselected women with adequat ovarian reserve entering for the first time in IVF programme were stimulated with corifollitropin alfa and GnRH antagonists. Avarage age in the study group was 32,8 years (29-42 years), women younger then 36 and less then 60 kg received Elonva 100 µg , all others (age > 36 let, weight > 60 kg) Elonva 150 µg. Five days after egg retrieval one blastocyst was transferred (single embryo transfer - eSET). Our results were compared with the resuls in higly selected groups of women from Phase III randomized trials. After stimulation with corifollitropin alfa and GnRH antagonists on average 10,6 (9,2 ± 4,2) eggs could be retrieved, among them 7,3 (6,6 ± 3,9) were M II oocytes (68,9%) and fertilisation rate was 84,6%. After first embryo transfer ("fresh" embryos and embryos from "freeze all" cycles) 14 pregnancies were achieved (37,8%), three pregnancies were achieved later from transfer of frozen-thawed embryos (cumulative pregnancy rate 45,9%). There were three abortions. No severe hyperstimulation syndrom occured. Our results in unselected group of women stimulated for the first in an IVF programme with corifollitropin alfa are fully comparable with results published in randomized trials with selected group of patiens. Corifollitropin alfa in combination with daily GnRH antagonist can be successfully used in normal-responder patients stimulated for the first time in an IVF programmeKeywords: corifollitropin alfa, GnRH antagonists, ovarian stimulation, pregnancy.

A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis.

PubMed

Loverro, Giuseppe; Carriero, Carmine; Rossi, A Cristina; Putignano, Giuseppe; Nicolardi, Vittorio; Selvaggi, Luigi

2008-02-01

To investigate the role of adjuvant treatment with gonadotropin-releasing-hormone agonist (GnRHa) following conservative surgical treatment of endometriosis. Sixty patients in the reproductive age (mean age 28.6 years), with symptomatic stages III and IV endometriosis following laparoscopic surgery and without previous hormonal treatment were enrolled in a prospective, randomized, controlled trial to compare the effects of 3-month treatment with triptorelin depot-3.75 i.m. (30 patients) versus expectant management using placebo injection (30 patients). Six patients (one in triptorelin group and five in placebo group) were lost at follow-up, the remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence, endometrioma relapses and pregnancy rate were evaluated during a 5-year follow-up. The results of 29 cases treated with triptorelin and 25 that received placebo did not show significant differences in pain recurrence (P=1, RR=0.94, 95% CI=0.57-1.55), endometrioma relapse (P=0.67, RR=1.29, 95% CI=0.66-2.50), and pregnancy rate in infertile women (P=0.80, RR=0.81, 95% CI=0.37-1.80). Curves of time of pain recurrence and pregnancy during 5-year follow-up did not show significant differences between the two groups (P=0.79 and P=0.51, respectively, using Mantel-Haenzsel logrank test). Triptorelin treatment after operative laparoscopy for stage III/IV endometriosis does not appear to be superior to expectant management in terms of prevention of symptoms recurrence and endometrioma relapse, and has no influence on pregnancy rate in endometriosis-associated infertility.

Ab initio random structure searching of organic molecular solids: assessment and validation against experimental data† †Electronic supplementary information (ESI) available: Results of similarity analysis between the 11 structures of lowest energy obtained in the AIRSS calculations and the reported structures of form III and form IV of m-ABA; unit cell parameters and volumes for all structures considered; comparison of 2θ values derived from the unit cell parameters of different structural models representing form III of m-ABA; Le Bail fitting of the experimental powder XRD pattern of form IV of m-ABA recorded at 70 K using, as the initial structural model, the reported crystal structure following geometry optimization; table of calculated (GIPAW) absolute isotropic NMR shieldings; simulated powder XRD data for the considered structures after precise geometry optimization; experimental 1H MAS NMR spectra of forms III and IV. (pdf) The calculated and experimental data for this study are provided as a supporting dataset from WRAP, the Warwick Research Archive Portal at http://wrap.warwick.ac.uk/91884. See DOI: 10.1039/c7cp04186a

PubMed Central

Zilka, Miri; Dudenko, Dmytro V.; Hughes, Colan E.; Williams, P. Andrew; Sturniolo, Simone; Franks, W. Trent; Pickard, Chris J.

2017-01-01

This paper explores the capability of using the DFT-D ab initio random structure searching (AIRSS) method to generate crystal structures of organic molecular materials, focusing on a system (m-aminobenzoic acid; m-ABA) that is known from experimental studies to exhibit abundant polymorphism. Within the structural constraints selected for the AIRSS calculations (specifically, centrosymmetric structures with Z = 4 for zwitterionic m-ABA molecules), the method is shown to successfully generate the two known polymorphs of m-ABA (form III and form IV) that have these structural features. We highlight various issues that are encountered in comparing crystal structures generated by AIRSS to experimental powder X-ray diffraction (XRD) data and solid-state magic-angle spinning (MAS) NMR data, demonstrating successful fitting for some of the lowest energy structures from the AIRSS calculations against experimental low-temperature powder XRD data for known polymorphs of m-ABA, and showing that comparison of computed and experimental solid-state NMR parameters allows different hydrogen-bonding motifs to be discriminated. PMID:28944393

The large-scale placebo-controlled beta-blocker studies in systolic heart failure revisited: results from CIBIS-II, COPERNICUS and SENIORS-SHF compared with stratified subsets from MERIT-HF.

PubMed

Wikstrand, J; Wedel, H; Castagno, D; McMurray, J J V

2014-02-01

The four pivotal beta-blocker trials in heart failure (HF) had different inclusion criteria, making comparison difficult without patient stratifying. The aim of this study was to compare, in similar patients, the effects of bisoprolol, metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol on (i) total mortality, (ii) all-cause mortality or hospitalization due to cardiovascular causes (time to first event), (iii) all-cause mortality or hospitalization because of HF and (iv) tolerability, defined as discontinuation of randomized treatment. We compared stratified (s ) subsets in MERIT-HF with patients in CIBIS-II [New York Heart Association (NYHA) class III/IV and ejection fraction (EF) ≤ 35%] and COPERNICUS (NYHA III/IV and EF <25%) and in patients with systolic HF in SENIORS-SHF (age ≥ 70 years and EF ≤ 35%). The annual mortality rates in the placebo and beta-blocker arms were: (i) CIBIS-II (n = 2647), 13.2% vs. 8.8% (relative risk reduction 34%, 95% CI: 19-46, P < 0.0001) and MERIT-HFs (n = 2002), 14.8% vs. 8.6% (relative risk reduction 42%, 95% CI: 24-56, P < 0.0001); (ii) COPERNICUS (n = 2289), 19.7% vs. 12.8% (relative risk reduction 35%, 95% CI: 19-48, P = 0.0014) and MERIT-HFs (n = 795), 19.1% vs. 11.7% (relative risk reduction 39%; 95% CI: 11-58, P = 0.0086); (iii) SENIORS-SHF (n = 1359), 11.3% vs. 9.7% (relative risk reduction 16%, NS) and MERIT-HFs (n = 985), 14.8% vs. 10.1% (relative risk reduction 32%, 95% CI: 2-53, P = 0.038). The effects on the other outcomes assessed were similar. Analyses indicated fewer discontinuations from randomized treatment on beta-blockers compared with placebo in COPERNICUS and the MERIT-HFs subsets. The efficacy and tolerability of bisoprolol, carvedilol and metoprolol CR/XL are similar in patients with systolic HF, irrespective of NYHA class or ejection fraction. Nebivolol is less effective and not better tolerated. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Treating Patients with High-Risk Smoldering Myeloma

Cancer.gov

In this phase III clinical trial, patients with smoldering myeloma classified as high risk for progression will be randomly assigned to undergo standard observation or six 4-week courses of treatment with the drug lenalidomide.

The effects of intravenous, enteral and combined administration of glutamine on malnutrition in sepsis: a randomized clinical trial.

PubMed

Koksal, Guniz Meyancı; Erbabacan, Emre; Tunali, Yusuf; Karaoren, Gulsah; Vehid, Suphi; Oz, Huseyin

2014-01-01

Our aim was to compare the effects of intravenous, enteral, and enteral plus intravenous supplemented glutamine on plasma transferrin, nitrogen balance, and creatinine/height index in septic patients with malnutrition. Blood and urine samples were collected for transferrin, urea and creatinine measurements. Samples, SOFA score and protein-calorie intake values were repeated on days 7 and 15. Patients (n:120) were randomly divided into 4 groups. Group I received 30 g/day IV glutamine, group II received 30 g/day enteral glutamine, group III received 15 g/day IV and 15 g/day enteral glutamine. Group IV received only enteral feeding as a control group. Transferrin levels decreased in group IV (p<0.01 0-7 days, p<0.01 7-15 days, p<0.01 0-15 days). Nitrogen balance levels were highest in group IV when compared with group I (p<0.05, p<0.001), group II (p<0.001), and group III (p<0.05, p<0.001) on days 7-15. Creatinine/height indexes increased in group I (p<0.001), group II (p<0.001), group III (p<0.001), and group IV (p<0.05) on day 15. In group III the creatinine/height index was higher than in groups I and II (p<0.05). In group IV, creatinine/height index was lower than in group I (p<0.01) and group II (p<0.001). Protein-calorie intake in group IV was higher than others on day 7 (p<0.05). SOFA scores of group IV were higher than the other groups on day 15 (p<0.05). This study demonstrated, that combined route of gln supplementation resulted in the most positive outcome to transferrin, creatine/height index and nitrogen balance (on days 7 and 15) during the catabolic phase of septic patients with malnutrition.

Validation of the 12-Gene Colon Cancer Recurrence Score in NSABP C-07 As a Predictor of Recurrence in Patients With Stage II and III Colon Cancer Treated With Fluorouracil and Leucovorin (FU/LV) and FU/LV Plus Oxaliplatin

PubMed Central

Yothers, Greg; O'Connell, Michael J.; Lee, Mark; Lopatin, Margarita; Clark-Langone, Kim M.; Millward, Carl; Paik, Soonmyung; Sharif, Saima; Shak, Steven; Wolmark, Norman

2013-01-01

Purpose Accurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07. Methods Recurrence Score was assessed in 892 fixed, paraffin-embedded tumor specimens (randomly selected 50% of patients with tissue). Data were analyzed by Cox regression adjusting for stage and treatment. Results Continuous Recurrence Score predicted recurrence (hazard ratio for a 25-unit increase in score, 1.96; 95% CI, 1.50 to 2.55; P < .001), as well as disease-free and overall survival (both P < .001). Recurrence Score predicted recurrence risk (P = .001) after adjustment for stage, mismatch repair, nodes examined, grade, and treatment. Recurrence Score did not have significant interaction with stage (P = .90) or age (P = .76). Relative benefit of oxaliplatin was similar across the range of Recurrence Score (interaction P = .48); accordingly, absolute benefit of oxaliplatin increased with higher scores, most notably in patients with stage II and IIIA/B disease. Conclusion The 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer. PMID:24220557

Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin.

PubMed

Yothers, Greg; O'Connell, Michael J; Lee, Mark; Lopatin, Margarita; Clark-Langone, Kim M; Millward, Carl; Paik, Soonmyung; Sharif, Saima; Shak, Steven; Wolmark, Norman

2013-12-20

Accurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07. Recurrence Score was assessed in 892 fixed, paraffin-embedded tumor specimens (randomly selected 50% of patients with tissue). Data were analyzed by Cox regression adjusting for stage and treatment. Continuous Recurrence Score predicted recurrence (hazard ratio for a 25-unit increase in score, 1.96; 95% CI, 1.50 to 2.55; P < .001), as well as disease-free and overall survival (both P < .001). Recurrence Score predicted recurrence risk (P = .001) after adjustment for stage, mismatch repair, nodes examined, grade, and treatment. Recurrence Score did not have significant interaction with stage (P = .90) or age (P = .76). Relative benefit of oxaliplatin was similar across the range of Recurrence Score (interaction P = .48); accordingly, absolute benefit of oxaliplatin increased with higher scores, most notably in patients with stage II and IIIA/B disease. The 12-gene Recurrence Score predicts recurrence risk in stage II and stage III colon cancer and provides additional information beyond conventional clinical and pathologic factors. Incorporating Recurrence Score into the clinical context may better inform adjuvant therapy decisions in stage III as well as stage II colon cancer.

Molecular targeted therapy in enteropancreatic neuroendocrine tumors: from biology to clinical practice.

PubMed

Fazio, N; Scarpa, A; Falconi, M

2014-01-01

Advanced enteropancreatic (EP) neuroendocrine tumors (NETs) can be treated with several different therapies, including chemotherapy, biotherapy, and locoregional treatments. Over the last few decades, impressive progress has been made in the biotherapy field. Three main druggable molecular targets have been studied and developed in terms of therapy: somatostatin receptor (sstr), mammalian target of rapamycin (mTOR), and angiogenic factors. In particular, research has moved from the old somatostatin analogs (SSAs), such as octreotide (OCT) and lanreotide (LAN), specifically binding to the sstr-2, to the newer pasireotide (PAS), which presents a wider sstr spectrum. Over the last ten years, several molecular targeted agents (MTAs) have been studied in phase II trials, and very few of them have reached phase III. The mTOR inhibitor everolimus and the multitargeted inhibitor sunitinib have been approved for clinical use by the FDA and EMA in advanced well/moderately-differentiated (WD, MD) progressive pancreatic neuroendocrine tumors (PNETs), on the basis of the positive results of two international large randomized phase III trials vs. placebo. Bevacizumab has been studied in a large US phase III trial vs. interferon (IFN)-alfa2b, and results are pending. In this review, the biological and clinical aspects of MTAs introduced into clinical practice or which are currently in an advanced phase of clinical investigation are addressed.

Assessing the Eligibility Criteria in Phase III Randomized Controlled Trials of Drug Therapy in Heart Failure With Preserved Ejection Fraction: The Critical Play-Off Between a "Pure" Patient Phenotype and the Generalizability of Trial Findings.

PubMed

Patel, Hitesh C; Hayward, Carl; Dungu, Jason N; Papadopoulou, Sofia; Saidmeerasah, Abdel; Ray, Robin; Di Mario, Carlo; Shanmugam, Nesan; Cowie, Martin R; Anderson, Lisa J

2017-07-01

To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival. We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice. Follow-up was available for a minimum of 24 months in each patient. Increasing the number of study eligibility criteria identifies a progressively smaller group of patients from real-life practice suitable for recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic patients would have been eligible, whereas the PARAGON-HF criteria significantly reduced this proportion to 32%. The patients identified from our clinical population had similar mortality rates using the different criteria, which were consistently higher than those reported in the actual clinic trials. Trial eligibility criteria have become stricter with time, which reduces the number of eligible patients, affecting both generalizability of any findings and feasibility of completing an adequately powered trial. We could not find evidence that the additional criteria used in more recent randomized trials in HFpEF have identified patients at higher risk of all-cause mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Enhancement of Analgesic Effect of Intrathecal Neostigmine by Intrathecal Clonidine and Transdermal Nitroglycerin Patch on Bupivacaine Spinal Anesthesia.

PubMed

Mammen, Mathew V; Tripathi, Manoj; Chandola, Harish C; Tyagi, Amit; Bais, Prateek Singh; Sanjeev, Om Prakash

2017-01-01

Relief of pain is very important goal intraoperatively and postoperatively. Neostigmine has been used successfully intrathecally with other agents such as clonidine and opioids for pain relief. This study aims to compare and evaluate the efficacy and safety of combining intrathecal (IT) neostigmine with IT clonidine and transdermal nitroglycerin (tNTG) patch for the relief of pain in patients after surgery. This was a randomized, prospective, and comparative study. In this study, recruited patients were randomly allocated into three groups. Groups I, II, and III received intrathecally 25 μg of neostigmine + 15 mg hyperbaric 0.5% bupivacaine, 25 μg of neostigmine + 25 μg clonidine + 15 mg hyperbaric 0.5% bupivacaine, and 25 μg of neostigmine + tNTG patch (3 cm × 5 cm, 5 mg/24 h) +15 mg hyperbaric 0.5% bupivacaine, respectively. Heart rate, mean arterial pressure, analgesic properties, and complications were assessed and compared among groups. Mean and standard deviation were calculated. Test of analysis between two groups was done by t -test and among three groups by ANOVA, then P value was calculated. Duration of analgesia was significantly longer in Group III in comparison to Group II (7.142 ± 1.81 vs. 4.408 ± 0.813 h) and was significantly longer in Group II in comparison to Group I (4.408 ± 0.813 vs. 2.583 ± 0.493 h). Analgesic requirement was significantly less in Group III in comparison to Group II (1.9 ± 0.76 vs. 2.5 ± 0.51) and was significantly less in Group II in comparison to Group I (2.5 ± 0.51 vs. 3.1 ± 0.48). Sedation score was found significantly high in Group II than other groups. Both IT clonidine and tNTG patch with bupivacaine + neostigmine spinal anesthesia were found effective in pain control. Results were found better with tNTG patch.

Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study*

PubMed Central

Rzany, B; Griffiths, T; Walker, P; Lippert, S; McDiarmid, J; Havlickova, B

2014-01-01

Summary Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. Objectives To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. Methods In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm−2) or placebo injections into their SMF at up to four treatment sessions ∽28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. Results Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm−2, respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS;P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS;P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. Conclusions ATX-101 was effective and well tolerated for nonsurgical SMF reduction. What's already known about this topic? Unwanted submental fat (SMF) is considered aesthetically unappealing. Liposuction and face-lift are effective treatments for SMF reduction but are invasive and not suitable for all patients, whereas nonsurgical alternatives lack robust clinical evidence related to their safety and efficacy. ATX-101, a proprietary formulation of synthetically derived deoxycholic acid, is the first nonsurgical treatment for SMF reduction to be investigated in randomized, placebo-controlled clinical studies. What does this study add? This study provides the first data from a large-scale, randomized, placebo-controlled, phase III study of an injectable therapy for SMF reduction in a field currently lacking a sound evidence base. ATX-101 was superior to placebo for the clinician- and patient-evaluated reduction of unwanted SMF and led to improved patient perception about their appearance. ATX-101 was well tolerated; treatment-associated adverse events were mainly transient and localized injection-site reactions. PMID:24147933

Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study.

PubMed

Boccia, Ralph V; Gordan, Lucio N; Clark, Gemma; Howell, Julian D; Grunberg, Steven M

2011-10-01

A novel transdermal formulation of granisetron (the granisetron transdermal delivery system (GTDS)) has been developed to deliver granisetron continuously over 7 days. This double-blind, phase III, non-inferiority study compared the efficacy and tolerability of the GTDS to daily oral granisetron for the control of chemotherapy-induced nausea and vomiting (CINV). Six hundred forty-one patients were randomized to oral (2 mg/day, 3-5 days) or transdermal granisetron (one GTDS patch, 7 days), before receiving multi-day chemotherapy. The primary endpoint was complete control of CINV (no vomiting/retching, no more than mild nausea, no rescue medication) from chemotherapy initiation until 24 h after final administration. The prespecified non-inferiority margin was 15%. Five hundred eighty-two patients were included in the per protocol analysis. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation. The GTDS provides effective, well-tolerated control of CINV associated with moderately or highly emetogenic multi-day chemotherapy. It offers a convenient alternative route for delivering granisetron for up to 7 days that is as effective as oral granisetron.

The efficacy of GMFM-88 and GMFM-66 to detect changes in gross motor function in children with cerebral palsy (CP): a literature review.

PubMed

Alotaibi, Madawi; Long, Toby; Kennedy, Elizabeth; Bavishi, Siddhi

2014-01-01

The purpose of this study was to review published research on the use of the Gross Motor Function Measure (GMFM-88) and (GMFM-66) as outcome measures to determine if these tools detect changes in gross motor function in children with cerebral palsy (CP) undergoing interventions. A comprehensive literature search was conducted using Medline and PubMed to identify studies published from January 2000 through January 2011 that reported the accuracy of GMFM-88 and GMFM-66 to measure changes over time in children with CP undergoing interventions. The keywords used for the search were "GMFM" and "CP". Two of the authors (M.A. and S.B.) reviewed the titles and abstracts found in the databases. The methodological quality of the studies was assessed by using the Critical Review Form-Quantitative Studies. Of 62 papers initially identified, 21 studies fulfilled the inclusion criteria. These articles consist of three longitudinal studies, six randomized controlled trials, four repeated measure design, six pre-post test design, a case series and one non-randomized prospective study. The included studies were generally of moderate to high methodological quality. The studies included children from a wide age range of 10 months to 16 years. According to the National Health and Medical Research Council, the study designs were level II, III-2, III-3 and IV. The review suggests that the GMFM-88 and GMFM-66 are useful as outcome measures to detect changes in gross motor function in children with CP undergoing interventions. Implications for Rehabilitation Accurate measurement of change in gross motor skill acquisition is important to determine effectiveness of intervention programs in children with cerebral palsy (CP). The Gross Motor Function Measure (GMFM-88 and GMFM-66) are common tools used by rehabilitation specialists to measure gross motor function in children with CP. The GMFM appears to be an effective outcome tool for measuring change in gross motor function according to a small number of randomized control studies utilizing participant populations of convenience.

Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study.

PubMed

Okubo, Kimihiro; Gotoh, Minoru; Asako, Mikiya; Nomura, Yasuyuki; Togawa, Michinori; Saito, Akihiro; Honda, Takayuki; Ohashi, Yoshihiro

2017-01-01

Bilastine, a novel non-sedating second-generation H 1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexofenadine (60 mg twice daily), or a matched placebo (double dummy) in patients with PAR. All patients were instructed to record individual nasal and ocular symptoms in diaries daily. The primary endpoint was the mean change in total nasal symptom scores (TNSS) from baseline to Week 2 (Days 10-13). A total of 765 patients were randomly allocated to receive bilastine, fexofenadine, or placebo (256, 254, and 255 patients, respectively). The mean change in TNSS from baseline at Week 2 was significantly decreased by bilastine (-0.98) compared to placebo (-0.63, P = 0.023). Bilastine and fexofenadine showed no significant difference in the primary endpoint. However, the mean change in TNSS from baseline on Day 1 was more significantly decreased by bilastine (-0.99) than by placebo (-0.28, P < 0.001) or fexofenadine (-0.62, P = 0.032). The active drugs also improved instantaneous TNSS 1 h after the first and before the second drug administration on Day 1 (P < 0.05). The study drugs were well tolerated. After 2-week treatment period, bilastine 20 mg once daily was effective and tolerable in Japanese patients with PAR, and exhibited a rapid onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Effect of More vs Less Frequent Follow-up Testing on Overall and Colorectal Cancer-Specific Mortality in Patients With Stage II or III Colorectal Cancer: The COLOFOL Randomized Clinical Trial.

PubMed

Wille-Jørgensen, Peer; Syk, Ingvar; Smedh, Kenneth; Laurberg, Søren; Nielsen, Dennis T; Petersen, Sune H; Renehan, Andrew G; Horváth-Puhó, Erzsébet; Påhlman, Lars; Sørensen, Henrik T

2018-05-22

Intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, but evidence of a survival benefit is limited. To examine overall mortality, colorectal cancer-specific mortality, and colorectal cancer-specific recurrence rates among patients with stage II or III colorectal cancer who were randomized after curative surgery to 2 alternative schedules for follow-up testing with computed tomography and carcinoembryonic antigen. Unblinded randomized trial including 2509 patients with stage II or III colorectal cancer treated at 24 centers in Sweden, Denmark, and Uruguay from January 2006 through December 2010 and followed up for 5 years; follow-up ended on December 31, 2015. Patients were randomized either to follow-up testing with computed tomography of the thorax and abdomen and serum carcinoembryonic antigen at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; n = 1253 patients) or at 12 and 36 months after surgery (low-frequency group; n = 1256 patients). The primary outcomes were 5-year overall mortality and colorectal cancer-specific mortality rates. The secondary outcome was the colorectal cancer-specific recurrence rate. Both intention-to-treat and per-protocol analyses were performed. Among 2555 patients who were randomized, 2509 were included in the intention-to-treat analysis (mean age, 63.5 years; 1128 women [45%]) and 2365 (94.3%) completed the trial. The 5-year overall patient mortality rate in the high-frequency group was 13.0% (161/1253) compared with 14.1% (174/1256) in the low-frequency group (risk difference, 1.1% [95% CI, -1.6% to 3.8%]; P = .43). The 5-year colorectal cancer-specific mortality rate in the high-frequency group was 10.6% (128/1248) compared with 11.4% (137/1250) in the low-frequency group (risk difference, 0.8% [95% CI, -1.7% to 3.3%]; P = .52). The colorectal cancer-specific recurrence rate was 21.6% (265/1248) in the high-frequency group compared with 19.4% (238/1250) in the low-frequency group (risk difference, 2.2% [95% CI, -1.0% to 5.4%]; P = .15). Among patients with stage II or III colorectal cancer, follow-up testing with computed tomography and carcinoembryonic antigen more frequently compared with less frequently did not result in a significant rate reduction in 5-year overall mortality or colorectal cancer-specific mortality. clinicaltrials.gov Identifier: NCT00225641.

From Clinical Trials to the Front Line: Vinflunine for Treatment of Urothelial Cell Carcinoma at the National Cancer Institute of Naples.

PubMed

Facchini, Gaetano; Della Pepa, Chiara; Cavaliere, Carla; Cecere, Sabrina C; Di Napoli, Marilena; D'Aniello, Carmine; Crispo, Anna; Iovane, Gelsomina; Maiolino, Piera; Tramontano, Teresa; Piscitelli, Raffaele; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Sorrentino, Domenico; Perdonà, Sisto; Pignata, Sandro

2016-01-01

The efficacy of Vinflunine, after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract, TCCU, has been demonstrated in an international, randomized, phase III trial comparing Vinflunine plus Best Supportive Care, BSC, with BSC alone. On the basis of that study vinflunine has been approved by the European Medicine Association, EMA, for treatment of TCCU patients after failure of a platinum treatment. However, since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring, "real life" experiences are very helpful to verify the efficacy of a new therapy. This was a spontaneous, observational, retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center, data about demographics, disease characteristics, and previous treatments were collected and outcome and toxicities of vinflunine were analyzed. 41 of 43 patients were eligible for RR analysis, the Overall RR was 12%, the Disease Control Rate was 29%; when including only patients treated in II line the DCR rose to 33%; the median PFS and the median OS were 2.2 and 6.9 months, respectively. Our findings were consistent with the outcome data emerged in the phase III randomized trial and in the other observational studies conducted all around Europe in the last 2-3 years. This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug.

Computational Sciences.

DTIC Science & Technology

1987-11-01

III. - 7 1 11 1*25 4 11 - IN, I 61I’. UNCLASSIFIED MASTER COPY - FOR REPRODUCTION PURPOSES ) C . AD-A 190 ’PORT DOCUMENTATION PAGE ~~ 190 826 lb...E uations, University of Alabama, Birmingham, *AL.-7 N. Medhin, M. Sambandham, and C . K. Zoltani, Numerical Solution to a System of Random Volterra...Sambandham, and C . K. Zoltani, "Numerical Solution to a System of Random Volterra Integral Equations I: Successive Approximation Method’,"-submitted to

Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: a randomised study.

PubMed

Torresi, Joseph; Heron, Leon G; Qiao, Ming; Marjason, Joanne; Chambonneau, Laurent; Bouckenooghe, Alain; Boaz, Mark; van der Vliet, Diane; Wallace, Derek; Hutagalung, Yanee; Nissen, Michael D; Richmond, Peter C

2015-09-22

The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicity of phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placebo in a dengue-naïve population. Healthy 18-60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three subcutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo, respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50 GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the third vaccination-equivalence among lots was demonstrated if the lower and upper limits of the two-sided 95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively. 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) participants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12 pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTs for serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively). Phase III lots can be produced in a consistent manner with predictable immune response and acceptable safety profile similar to previously characterised phase II lots. The phase III lots may be considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4 across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTs observed in the phase III lots were consistently higher than those for the phase II lot. As such, in our view, biological equivalence for all serotypes was demonstrated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

How much incisor decompensation is achieved prior to orthognathic surgery?

PubMed

McNeil, Calum; McIntyre, Grant T; Laverick, Sean

2014-07-01

To quantify incisor decompensation in preparation for orthognathic surgery. Pre-treatment and pre-surgery lateral cephalograms for 86 patients who had combined orthodontic and orthognathic treatment were digitised using OPAL 2.1 [http://www.opalimage.co.uk]. To assess intra-observer reproducibility, 25 images were re-digitised one month later. Random and systematic error were assessed using the Dahlberg formula and a two-sample t-test, respectively. Differences in the proportions of cases where the maxillary (1100 +/- 60) or mandibular (900 +/- 60) incisors were fully decomensated were assessed using a Chi-square test (p<0.05). Mann-Whitney U tests were used to identify if there were any differences in the amount of net decompensation for maxillary and mandibular incisors between the Class II combined and Class III groups (p<0.05). Random and systematic error were less than 0.5 degrees and p<0.05, respectively. A greater proportion of cases had decompensated mandibular incisors (80%) than maxillary incisors (62%) and this difference was statistically significant (p=0.029). The amount of maxillary incisor decompensation in the Class II and Class III groups did not statistically differ (p=0.45) whereas the mandibular incisors in the Class III group underwent statistically significantly greater decompensation (p=0.02). Mandibular incisors were decompensated for a greater proportion of cases than maxillary incisors in preparation for orthognathic surgery. There was no difference in the amount of maxillary incisor decompensation between Class II and Class III cases. There was a greater net decompensation for mandibular incisors in Class III cases when compared to Class II cases. Key words:Decompensation, orthognathic, pre-surgical orthodontics, surgical-orthodontic.

A randomized, double-blind, controlled trial of add-on therapy in moderate-to-severe Parkinson's disease.

PubMed

Zhao, Shifu; Cheng, Rongchuan; Zheng, Jian; Li, Qianning; Wang, Jingzhou; Fan, Wenhui; Zhang, Lili; Zhang, Yanling; Li, Hongzeng; Liu, Shuxiao

2015-10-01

The primary objective was to evaluate the efficacy and safety of droxidopa as add-on therapy in improving stiffness, tremors and other motor functions and activities of daily living for moderate-to-severe Parkinson's disease (PD). PD patients, above Hoehn-Yahr III (including Hoehn-Yahr III), were randomly assigned to drug therapy (droxidopa 600 mg/day for 8 weeks) or placebo. Efficacy indicators were the Unified Parkinson's Disease Rating Scale (UPDRS) part I, II, III subscale, Clinical Global Impression (CGI) rating score, and individual symptom scores (e.g. stiffness, tremors), to evaluate motor function and activities of daily life. There are 109 patients in the droxidopa group, and 110 in the placebo group, at baseline, there were no differences between the two groups for age, body weight, disease severity and previous drugs therapy. At days 14 and 57 of droxidopa add on treatment, UPDRS-II scores reflecting activities of daily life and UPDRS-III scores reflecting motor functions were significantly different compared to the pre-treatment baseline scores (P < 0.01), UPDRS- II and UPDRS-III scores at day 14 and day 57 were also significantly different (P < 0.01) between the two groups. Individual motor symptoms such as stiffness, resting tremor, and alternate hand motion were also significantly improved with droxidopa on days 14 and 57 of treatment (P < 0.01 vs placebo), showing that droxidopa is effective in improving rigidity, tremor and alternate motion of hand. Droxidopa was effective as symptomatic adjunct therapy, improved significantly motor function and activities of daily living, benefited patients with signs of tremor and Stiffness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Action of Brazilian propolis on hematological and serum biochemical parameters of Blue-fronted Amazons (Amazona aestiva, Linnaeus, 1758) in captivity.

PubMed

Silva, Cínthia R B; Putarov, Thaila C; Fruhvald, Erika; Destro, Flavia C; Marques Filho, Wolff C; Thomazini, Camila M; Barbosa, Tatiana S; Orsi, Ricardo O; Siqueira, Edson R

2014-07-01

The present study aimed to evaluate the effect of propolis use on hematological and serum biochemical parameters in Blue-fronted Amazons (Amazona aestiva). For this, 12 adult birds were distributed randomly into individual cages, divided into treatments with different propolis levels (A = 0.0%; B = 0.5%; and C = 1.0%), in 3 distinct phases (I, II, and III), with 15-d duration for phases I and III and 30 d for phase II, totaling 60 d. In phases I and III, all birds received treatment A ration, and in phase II received A, B, or C (4 birds per treatment). At the end of each phase, blood was collected for biochemical and hematological evaluations. The variables were analyzed by ANOVA (P < 0.05). Results suggest that 0.5% propolis reduced lactate dehydrogenase levels, whereas treatment B augmented hemoglobin concentrations and eosinophil count. It is concluded that 0.5% propolis improves levels of lactate dehydrogenase, hemoglobin, and eosinophils. © 2014 Poultry Science Association Inc.

Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

Cancer.gov

Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

Geographical distribution of genetic polymorphism of the pathogen Histoplasma capsulatum isolated from infected bats, captured in a central zone of Mexico.

PubMed

Taylor, Maria Lucia; Chávez-Tapia, Catalina B; Rojas-Martínez, Alberto; del Rocio Reyes-Montes, Maria; del Valle, Mirian Bobadilla; Zúñiga, Gerardo

2005-09-01

Fourteen Histoplasma capsulatum isolates recovered from infected bats captured in Mexican caves and two human H. capsulatum reference strains were analyzed using random amplification of polymorphic DNA PCR-based and partial DNA sequences of four genes. Cluster analysis of random amplification of polymorphic DNA-patterns revealed differences for two H. capsulatum isolates of one migratory bat Tadarida brasiliensis. Three groups were identified by distance and maximum-parsimony analyses of arf, H-anti, ole, and tub1 H. capsulatum genes. Group I included most isolates from infected bats and one clinical strain from central Mexico; group II included the two isolates from T. brasiliensis; the human G-217B reference strain from USA formed an independent group III. Isolates from group II showed diversity in relation to groups I and III, suggesting a different H. capsulatum population.

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design.

PubMed

Pujade-Lauraine, Eric; Fujiwara, Keiichi; Dychter, Samuel S; Devgan, Geeta; Monk, Bradley J

2018-03-27

Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in multiple solid tumors. Here, we describe the rationale and design for JAVELIN Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the role of checkpoint inhibition in women with ovarian cancer. This three-arm trial is comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian, fallopian tube or peritoneal cancer. Eligible patients are not preselected based on PD-L1 expression and may have received up to three prior lines of chemotherapy for platinum-sensitive disease, but none for resistant disease. Overall survival and progression-free survival are primary end points, and secondary end points include biomarker evaluations and pharmacokinetics.

Bevacizumab in ovarian cancer: A critical review of phase III studies

PubMed Central

Rossi, Luigi; Verrico, Monica; Zaccarelli, Eleonora; Papa, Anselmo; Colonna, Maria; Strudel, Martina; Vici, Patrizia; Bianco, Vincenzo; Tomao, Federica

2017-01-01

Bevacizumab (BV) is a humanized monoclonal antibody targeting vascular endothelial growth factor and it is the first molecular-targeted agent to be used for the treatment of ovarian cancer (OC). Randomized Phase III trials evaluated the combination of BV plus standard chemotherapy for first-line treatment of advanced OC and for platinum-sensitive and platinum-resistant recurrent OC. These trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, BV effectively improved the quality of life with regard to abdominal symptoms in recurrent OC patients. Bevacizumab is associated with adverse events such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed. This review describes the latest evidence for BV treatment of OC and selection of patients for personalized treatment. PMID:27852039

Critical Behaviors in Contagion Dynamics.

PubMed

Böttcher, L; Nagler, J; Herrmann, H J

2017-02-24

We study the critical behavior of a general contagion model where nodes are either active (e.g., with opinion A, or functioning) or inactive (e.g., with opinion B, or damaged). The transitions between these two states are determined by (i) spontaneous transitions independent of the neighborhood, (ii) transitions induced by neighboring nodes, and (iii) spontaneous reverse transitions. The resulting dynamics is extremely rich including limit cycles and random phase switching. We derive a unifying mean-field theory. Specifically, we analytically show that the critical behavior of systems whose dynamics is governed by processes (i)-(iii) can only exhibit three distinct regimes: (a) uncorrelated spontaneous transition dynamics, (b) contact process dynamics, and (c) cusp catastrophes. This ends a long-standing debate on the universality classes of complex contagion dynamics in mean field and substantially deepens its mathematical understanding.

Designing and conducting a randomized trial for pandemic critical illness: the 2009 H1N1 influenza pandemic.

PubMed

Annane, Djillali; Antona, Marion; Lehmann, Blandine; Kedzia, Cecile; Chevret, Sylvie

2012-01-01

To analyze the hurdles in implementing a randomized trial of corticosteroids for severe 2009 H1N1 influenza infections. This was an investigator-led, multicenter, randomized, placebo-controlled, double-blind trial of corticosteroids in ICU patients with 2009 H1N1 influenza pneumonia requiring mechanical ventilation. The feasibility of and hurdles in designing and initiating a phase III trial in a short-lived pandemic crisis were analyzed. The regulatory agency and ethics committee approved the study's scientific, financial, and ethical aspects within 4 weeks. Hydrocortisone and placebo were prepared centrally and shipped to participating hospitals within 6 weeks. The inclusion period started on November 9, 2009. From August 1, 2009 to March 8, 2010, only 205/224 ICU patients with H1N1 infections required mechanical ventilation. The peak of the wave was missed by 2-3 weeks and only 26 patients were randomized. The two main reasons for non-inclusion were patients' admission before the beginning of the trial and ICU personnel overwhelmed by clinical duties. Parallel rather than sequential regulatory and ethics approval, and preparation and masking of study drugs by local pharmacists would have allowed the study to start 1 month earlier and before the peak of the "flu" wave. A dedicated research team in each participating center would have increased the ratio of screened to randomized patients. This report highlights the main hurdles in implementing a randomized trial for a pandemic critical illness and proposes solutions for future trials.

Practical management of patients with myelofibrosis receiving ruxolitinib.

PubMed

Harrison, Claire; Mesa, Ruben; Ross, David; Mead, Adam; Keohane, Clodagh; Gotlib, Jason; Verstovsek, Srdan

2013-10-01

Myelofibrosis (MF) is characterized by bone marrow fibrosis, progressive anemia and extramedullary hematopoiesis, primarily manifested as splenomegaly. Patients also experience debilitating constitutional symptoms, including sequelae of splenomegaly, night sweats and fatigue. Ruxolitinib (INC424, INCB18424, Jakafi, Jakavi), a JAK1 and JAK2 inhibitor, was approved in November 2011 by the US FDA for the treatment of intermediate- or high-risk MF, and more recently in Europe and Canada for the treatment of MF-related splenomegaly or symptoms. These approvals were based on data from two randomized Phase III studies: COMFORT-I randomized against placebo, and COMFORT-II randomized against best available therapy. In these studies, ruxolitinib rapidly improved multiple disease manifestations of MF, reducing splenomegaly and improving quality of life of patients and potentially prolonging survival. However, as with other chemotherapies, ruxolitinib therapy is associated with some adverse events, such as anemia and thrombocytopenia. The aims of this article are to provide a brief overview of ruxolitinib therapy, to discuss some common adverse events associated with ruxolitinib therapy and to provide clinical management recommendations to maximize patients' benefit from ruxolitinib.

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial.

PubMed

Breugom, A J; van Gijn, W; Muller, E W; Berglund, Å; van den Broek, C B M; Fokstuen, T; Gelderblom, H; Kapiteijn, E; Leer, J W H; Marijnen, C A M; Martijn, H; Meershoek-Klein Kranenbarg, E; Nagtegaal, I D; Påhlman, L; Punt, C J A; Putter, H; Roodvoets, A G H; Rutten, H J T; Steup, W H; Glimelius, B; van de Velde, C J H

2015-04-01

The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME). The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual. Dutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Comparison of Electrotherapy, Rubber Band Ligation and Hemorrhoidectomy in the Treatment of Hemorrhoids: A Clinical and Manometric Study

PubMed Central

Izadpanah, A; Hosseini, SV; Mahjoob, M

2010-01-01

BACKGROUND Treatment of hemorrhoid disease is one of the most challenging fields in general surgery in which different methods are used to treat this condition. In this study, we compared the manometric and clinical results of three treatment methods for hemorrhoids. METHODS A total of 150 patients with symptomatic grades II or III internal hemorrhoids were randomly assigned to three groups. Group A underwent Ferguson hemorrhoidectomy, group B were treated with rubber band ligation (RBL) and group C were treated with direct current electrotherapy. RESULTS Preoperatively, grade III hemorrhoids had significantly higher mean resting pressure and mean squeezing pressure in comparison to grade II hemorrhoids. After hemorrhoidectomy, patients in group A had a significant decrease in the maximum resting pressure (90.8 to 77.7 mmHg) and maximum squeezing pressure (130.6 to 114.8 mmHg) with a significant raise in the volume of the first sensation. However there was no significant change in manometric indexes after RBL and electrotherapy. Group A patients had more postoperative pain and itching compared to groups B and C. CONCLUSION We conclude that electrotherapy is a safe, effective and simple method of treating grades II and III uncomplicated internal hemorrhoids. This procedure is associated with little postoperative pain and complications, and has the least changes in anorectal manometric characteristics. Therefore electrotherapy may be recommended as a treatment of choice for grades II and III uncomplicated internal hemorrhoids. PMID:25197506

Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels

PubMed Central

2010-01-01

Background Both apolipoprotein (Apo) C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG) levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128) polymorphism and alcohol consumption on serum TG levels. Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Results Serum total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C), ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P < 0.05-0.001). There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, low-density lipoprotein cholesterol (LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype (P < 0.01 for all). Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, HDL-C and ApoA-I levels in CC genotype, TC, HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC, TG, LDL-C, ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers (P < 0.05-0.01). But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers (P < 0.01). Multivariate logistic regression analysis showed that the levels of TC, TG and ApoB were correlated with genotype in nondrinkers (P < 0.05 for all). The levels of TC, LDL-C and ApoB were associated with genotype in drinkers (P < 0.01 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both groups. Conclusions This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG. PMID:20716347

Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels.

PubMed

Ruixing, Yin; Yiyang, Li; Meng, Li; Kela, Li; Xingjiang, Long; Lin, Zhang; Wanying, Liu; Jinzhen, Wu; Dezhai, Yang; Weixiong, Lin

2010-08-17

Both apolipoprotein (Apo) C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG) levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128) polymorphism and alcohol consumption on serum TG levels. A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Serum total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C), ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P < 0.05-0.001). There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, low-density lipoprotein cholesterol (LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype (P < 0.01 for all). Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, HDL-C and ApoA-I levels in CC genotype, TC, HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC, TG, LDL-C, ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers (P < 0.05-0.01). But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers (P < 0.01). Multivariate logistic regression analysis showed that the levels of TC, TG and ApoB were correlated with genotype in nondrinkers (P < 0.05 for all). The levels of TC, LDL-C and ApoB were associated with genotype in drinkers (P < 0.01 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both groups. This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG.

Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

PubMed

Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

2013-12-02

Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Prospective, Randomized Trial of Intravenous Hydroxocobalamin Versus Whole Blood Transfusion Compared to No Treatment for Class III Hemorrhagic Shock Resuscitation in a Prehospital Swine Model

DTIC Science & Technology

2015-03-01

statistically significant increase in systemic vascular resistance compared to control, but not whole blood, with a concomitant decrease in cardiac...increasing blood pressure as well as sys- temic vascular resistance in a hypovolemic hemorrhagic swine model.18 The primary hypothesis of this study is...output, sys- temic vascular resistance , mixed venous oxygen satura- tion, central venous pressure, pulmonary artery pressure, and core temperature. The

Therapeutic effectiveness of Ageratina pichinchensis on the treatment of chronic interdigital tinea pedis: a randomized, double-blind clinical trial.

PubMed

Romero-Cerecero, Ofelia; Zamilpa, Alejandro; Jiménez-Ferrer, Enrique; Tortoriello, Jaime

2012-06-01

Interdigital tinea pedis is the most frequent presentation, as well as the most severe clinical form of tinea pedis, constituting a therapeutic challenge. The aim of the study was to evaluate the effectiveness and tolerability of two concentrations of Ageratina pichinchensis extract (encecalin content, 0.76 and 1.52%, respectively) on patients with clinical and mycological diagnosis of chronic interdigital tinea pedis. By means of a randomized, double-blind clinical trial, three groups of patients were treated topically for 4 weeks with a cream containing the following: Group I-the lower concentration of A. pichinchensis extract, group II-the higher concentration, group III-2% ketoconazole. One hundred and sixty (160) ambulatory patients of either sex between the ages of 18 and 65 years were enrolled. The primary outcome variables were: clinical effectiveness, mycological effectiveness, therapeutic cure, tolerability, and treatment compliance. The secondary outcome variable was therapeutic success. At the end of treatment, therapeutic cure was achieved by 34.1, 41.8, and 39.53% of Groups I, II, and III, respectively. No statistical difference between the groups was observed. Both treatments were effective for the treatment of interdigital-type tinea pedis, while better results were observed on patients that received the higher concentration of the extract.

Octreotide inhibits hepatic fibrosis, bile duct proliferation and bacterial translocation in obstructive jaundice.

PubMed

Türkçapar, Nuran; Bayar, Sancar; Koyuncu, Ayhan; Ceyhan, Koray

2003-01-01

The protective effect of octreotide on bacterial translocation, bile duct epithelial proliferation and hepatic fibrosis was studied in an experimental obstructive jaundice model. Forty-five healthy Wistar albino rats were randomly divided into three groups. Group I (n = 15): Median laparotomy and common bile duct manipulation performed (Sham group). Group II (n = 15): Laparotomy and common bile duct ligation performed. Group III (n = 15): After laparotomy and common bile duct ligation octreotide (Sandostatin, sandoz) was given. Simultaneously group I and II received 3 cc 0.9% NaCl and group III received 20 micrograms/kg/daily octreotide subcutaneously every 8 hours during 9 days. Two days after the procedure all rats were opened under ether anesthesia and sterile conditions. Group I had simple laparotomy but group II and III also had common bile duct ligation by 5/0 prolene. Seven days after the surgery (9th day after treatment) all rats underwent laparotomy and tests for bacterial translocation, liver biochemical tests and histopathologic analysis of liver and small bowel were carried out. In group II cecal population levels of bacteria were significantly higher than group I and group III (p < 0.05). In group II there was also statistically significant bacterial translocation to the mesenteric lymph nodes. Pathological changes were found in terminal ileum samples in group II which seemed to improve in group III. Hepatocyte function was preserved with octreotide treatment which also significantly decreased bile duct proliferation and periportal fibrosis in response to biliary obstruction. This experimental study showed that octreotide is effective in preventing bacterial translocation, bile duct proliferation and hepatic fibrosis in obstructive jaundice.

Efficacy and safety of a biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL2) in treating de novo coronary artery disease: A pooled analysis of the CREDIT II and CREDIT III trials.

PubMed

Wang, Geng; Wang, Heyang; Xu, Bo; Yang, Yuejin; Yang, Zhiming; Li, Hui; Zhang, Zheng; Wang, Haichang; Yang, Lixia; Han, Yaling

2017-03-01

The safety and efficacy of the second-generation biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL2) in daily clinical practice remains unknown. Additionally, to meet the China Food and Drug Administration requirements, we conducted an objective performance criterion study from the CREDIT II and CREDIT III trials. CREDIT II was a randomized trial comparing the EXCEL2 versus EXCEL stent in patients with up to 2 de novo coronary lesions. CREDIT III was a prospective, single-arm study evaluating the efficacy and safety of EXCEL2 in broad types of de novo coronary artery lesions. This pooled analysis included patients in the CREDIT III and EXCEL2 arm of the CREDIT II trial. The primary outcome was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinical indicated target lesion revascularization (CI-TLR). The patient-oriented composite endpoint (PoCE) of all-cause death, all MI, or any revascularization was also analyzed. A total of 833 patients were included, consisting of 625 in the CREDIT III trial and 208 in the EXCEL2 arm of the CREDIT II trial. Twelve-month TLF occurred in 6.1% patients, cardiac death in 0.4%, TV-MI in 5%, and CI-TLR in 1.1%. Additionally, 64 (7.7%) PoCE and 3 probable late stent thromboses (0.4%) were recorded. EXCEL2 stent met the objective performance criterion on efficacy and safety with a low level of 12-month TLF as well as stent thrombosis when treating patients with de novo coronary lesions. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

No association of coffee consumption with gastric ulcer, duodenal ulcer, reflux esophagitis, and non-erosive reflux disease: a cross-sectional study of 8,013 healthy subjects in Japan.

PubMed

Shimamoto, Takeshi; Yamamichi, Nobutake; Kodashima, Shinya; Takahashi, Yu; Fujishiro, Mitsuhiro; Oka, Masashi; Mitsushima, Toru; Koike, Kazuhiko

2013-01-01

Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.

Nanoscale assembly of silicon-like [Al(As1-xNx)]ySi5-2y alloys: Fundamental theoretical and experimental studies of structural and optical properties

NASA Astrophysics Data System (ADS)

Jiang, L.; Sims, P. E.; Grzybowski, G.; Beeler, R. T.; Chizmeshya, A. V. G.; Smith, D. J.; Kouvetakis, J.; Menéndez, J.

2013-07-01

Ab initio theoretical simulations of Al(As1-xNx)Si3 alloys, a new class of optoelectronic materials, confirm that these compounds are likely to be disordered via a mechanism that preserves the integrity of the constituent III-V-Si3 tetrahedra but randomizes their orientation in the average diamond lattice of the compound. This type of disorder is consistent with experimental structural data and with the proposed growth mechanism for such alloys, according to which “III:V(SiH3)3” intermediate complexes are formed in the gas phase from reactions between group-III atomic beams and V(SiH3)3 molecules, delivering the entire III-V-Si3 tetrahedra to the growing film. Experimental optical studies of these Al(As1-xNx)Si3 alloys as well as more general [Al(As1-xNx)]ySi5-2y compounds grown on Si substrates were carried out using spectroscopic ellipsometry. The resulting dielectric functions are found to be similar to broadened versions of their counterparts in pure Si. This broadening may have important practical applications, particularly in photovoltaics, because it dramatically enhances the optical absorption of Si in the visible range of the electromagnetic spectrum. A critical point analysis reveals the existence of direct optical transitions at energies as low as 2.5 eV, well below the lowest direct absorption edge of Si at 3.3 eV. Such transitions are predicted theoretically for perfectly ordered III-V-Si3 compounds, and the experimental results suggest that they are robust against tetrahedra orientational disorder.

Cetuximab Plus Oxaliplatin May Not Be Effective Primary Treatment for Metastatic Colorectal Cancer

Cancer.gov

In a randomized phase III trial, the addition of the targeted therapy cetuximab to oxaliplatin and fluoropyrimidine chemotherapy did not prolong survival or time to disease progression of patients with advanced colorectal cancer.

Preventing Second Cancers in Colon Cancer Survivors

Cancer.gov

In this phase III trial, people who have had curative surgery for colon cancer will be randomly assigned to take sulindac and a placebo, eflornithine and a placebo, both sulindac and eflornithine, or two placebo pills for 36 months.

Redefining Adjuvant Therapy for Colon Cancer

Cancer.gov

In this trial, patients with resected stage III colon cancer are being randomly assigned to receive FOLFOX chemotherapy for either 3 or 6 months and to take either a pill called celecoxib or a matching placebo pill for 3 years.

Graphic Simulations of the Poisson Process.

DTIC Science & Technology

1982-10-01

RANDOM NUMBERS AND TRANSFORMATIONS..o......... 11 Go THE RANDOM NUMBERGENERATOR....... .oo..... 15 III. POISSON PROCESSES USER GUIDE....oo.ooo ......... o...again. In the superimposed mode, two Poisson processes are active, each with a different rate parameter, (call them Type I and Type II with respective...occur. The value ’p’ is generated by the following equation where ’Li’ and ’L2’ are the rates of the two Poisson processes ; p = Li / (Li + L2) The value

Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial†

PubMed Central

Skorupski, K. A.; Uhl, J. M.; Szivek, A; Allstadt Frazier, S. D.; Rebhun, R. B.; Rodriguez, C. O.

2016-01-01

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. PMID:24118677

Steroid treatment of acute graft-versus-host disease grade I: a randomized trial.

PubMed

Bacigalupo, Andrea; Milone, Giuseppe; Cupri, Alessandra; Severino, Antonio; Fagioli, Franca; Berger, Massimo; Santarone, Stella; Chiusolo, Patrizia; Sica, Simona; Mammoliti, Sonia; Sorasio, Roberto; Massi, Daniela; Van Lint, Maria Teresa; Raiola, Anna Maria; Gualandi, Francesca; Selleri, Carmine; Sormani, Maria Pia; Signori, Alessio; Risitano, Antonio; Bonifazi, Francesca

2017-12-01

Patients with acute graft- versus -host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II-IV GvHD. The cumulative incidence of grade II-IV GvHD was 50% in the observation arm and 33% in the treatment arm ( P =0.005). However, grade III-IV GvHD was comparable (13% vs 10%, respectively; P =0.6), and this was true for sibling and alternative donor transplants. Moderate/severe chronic GvHD was also comparable (17% vs 9%). In multivariate analysis, an early interval between transplant and randomization (

Feasibility study from a randomized controlled trial of standard closure of a stoma site vs biological mesh reinforcement.

PubMed

2016-09-01

Hernia formation occurs at closed stoma sites in up to 30% of patients. The Reinforcement of Closure of Stoma Site (ROCSS) randomized controlled trial is evaluating whether placement of biological mesh during stoma closure safely reduces hernia rates compared with closure without mesh, without increasing surgical or wound complications. This paper aims to report recruitment, deliverability and safety from the internal feasibility study. A multicentre, patient and assessor blinded, randomized controlled trial, delivered through surgical trainee research networks. A 90-patient internal feasibility study assessed recruitment, randomization, deliverability and early (30 day) safety of the novel surgical technique (ClinicalTrials.gov registration number NCT02238964). The feasibility study recruited 90 patients from the 104 considered for entry (45 to mesh, 45 to no mesh). Seven of eight participating centres randomized patients within 30 days of opening. Overall, 41% of stomas were created for malignant disease and 73% were ileostomies. No mesh-specific complications occurred. Thirty-one postoperative adverse events were experienced by 31 patients, including surgical site infection (9%) and postoperative ileus (6%). One mesh was removed for re-access to the abdominal cavity, for reasons unrelated to the mesh. Independent review by the Data Monitoring and Ethics Committee of adverse event data by treatment allocation found no safety concerns. Multicentre randomization to this trial of biological mesh is feasible, with no early safety concerns. Progression to the full Phase III trial has continued. ROCSS shows that trainee research networks can efficiently develop and deliver complex interventional surgical trials. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

A randomized, multi-center, open-label, phase III study of once-per-cycle DA-3031, a pegylated G-CSF, in comparison with daily filgrastim in patients receiving TAC chemotherapy for breast cancer.

PubMed

Park, K H; Lee, S; Park, J H; Kang, S Y; Kim, H Y; Park, I H; Park, Y H; Im, Y H; Lee, H J; Park, S; Lee, S I; Jung, K H; Kim, Y S; Seo, Jae Hong

2017-02-01

This multi-center, randomized, phase III study was conducted to demonstrate the non-inferiority of DA-3031 compared with daily filgrastim in patients during the first cycle of chemotherapy for breast cancer in terms of the duration of severe neutropenia (DSN). Seventy-four patients with breast cancer who were receiving combination chemotherapy with docetaxel, doxorubicin, and cyclophosphamide (TAC) were enrolled. All participants were randomized to receive either daily subcutaneous injections of filgrastim 100 μg/m 2 /day for up to 10 days or a single subcutaneous injection of DA-3031 at fixed doses of 6 mg on day 2 of each chemotherapy cycle. The mean duration of grade 4 (G4) neutropenia in cycle 1 was 2.08 ± 0.85 days for the filgrastim group and 2.28 ± 1.14 days for the DA-3031 group. The difference between groups was 0.2 ± 1.10 days (95 % confidence interval (CI) = -0.26, 0.66), which supported non-inferiority. No statistically significant differences were observed in nadir absolute neutrophil count (ANC) (154.34/mm 3 and 161.75/mm 3 for the filgrastim and DA-3031 groups, respectively; P = 0.8414) or in time to ANC recovery (10.03 ± 0.75 and 9.83 ± 1.56 days in the filgrastim and DA-3031 groups, respectively; P = 0.0611) during cycle 1. Serious AEs occurred in six (15.8 %) patients receiving filgrastim and in ten (27.8 %) patients receiving DA-3031; however, none was determined to be related to the study drug. DA-3031 and daily filgrastim are similar in regard to DSN and safety in breast cancer patients receiving TAC chemotherapy.

Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: Subset analysis of randomized trial intergroup SWOG S9704

PubMed Central

Puvvada, Soham D.; Stiff, Patrick J.; Leblanc, Michael; Cook, James R.; Couban, Stephen; Leonard, John P.; Kahl, Brad; Marcellus, Deborah; Shea, Thomas C.; Winter, Jane N.; Li, Hongli; Rimsza, Lisa M.; Friedberg, Jonathan W.; Smith, Sonali M.

2016-01-01

Summary Double hit lymphoma (DHL) and double protein-expressing (MYC and BCL2) lymphomas (DPL) fare poorly with R-CHOP; consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/−R with or without ASCT allows evaluation of intensive consolidation. Immunohistochemical analysis identified 27 of 198 patients (13.6%) with MYC IHC overexpression and 20 (74%) harboring concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median follow-up 127 months, there is a trend favoring outcomes after consolidative ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT. PMID:27072903

The Positive Emotions after Acute Coronary Events behavioral health intervention: Design, rationale, and preliminary feasibility of a factorial design study.

PubMed

Huffman, Jeffery C; Albanese, Ariana M; Campbell, Kirsti A; Celano, Christopher M; Millstein, Rachel A; Mastromauro, Carol A; Healy, Brian C; Chung, Wei-Jean; Januzzi, James L; Collins, Linda M; Park, Elyse R

2017-04-01

Positive psychological constructs, such as optimism, are associated with greater participation in cardiac health behaviors and improved cardiac outcomes. Positive psychology interventions, which target psychological well-being, may represent a promising approach to improving health behaviors in high-risk cardiac patients. However, no study has assessed whether a positive psychology intervention can promote physical activity following an acute coronary syndrome. In this article we will describe the methods of a novel factorial design study to aid the development of a positive psychology-based intervention for acute coronary syndrome patients and aim to provide preliminary feasibility data on study implementation. The Positive Emotions after Acute Coronary Events III study is an optimization study (planned N = 128), subsumed within a larger multiphase optimization strategy iterative treatment development project. The goal of Positive Emotions after Acute Coronary Events III is to identify the ideal components of a positive psychology-based intervention to improve post-acute coronary syndrome physical activity. Using a 2 × 2 × 2 factorial design, Positive Emotions after Acute Coronary Events III aims to: (1) evaluate the relative merits of using positive psychology exercises alone or combined with motivational interviewing, (2) assess whether weekly or daily positive psychology exercise completion is optimal, and (3) determine the utility of booster sessions. The study's primary outcome measure is moderate-to-vigorous physical activity at 16 weeks, measured via accelerometer. Secondary outcome measures include psychological, functional, and adherence-related behavioral outcomes, along with metrics of feasibility and acceptability. For the primary study outcome, we will use a mixed-effects model with a random intercept (to account for repeated measures) to assess the main effects of each component (inclusion of motivational interviewing in the exercises, duration of the intervention, and inclusion of booster sessions) from a full factorial model controlling for baseline activity. Similar analyses will be performed on self-report measures and objectively-measured medication adherence over 16 weeks. We hypothesize that the combined positive psychology and motivational interviewing intervention, weekly exercises, and booster sessions will be associated with superior physical activity. Thus far, 78 participants have enrolled, with 72% of all possible exercises fully completed by participants. The Positive Emotions after Acute Coronary Events III study will help to determine the optimal content, intensity, and duration of a positive psychology intervention in post-acute coronary syndrome patients prior to testing in a randomized trial. This study is novel in its use of a factorial design within the multiphase optimization strategy framework to optimize a behavioral intervention and the use of a positive psychology intervention to promote physical activity in high-risk cardiac patients.

Design of a phase III multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across diverse transmission settings in Africa

PubMed Central

2011-01-01

Background GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative are working in partnership to develop a malaria vaccine to protect infants and children living in malaria endemic regions of sub-Saharan Africa, which can be delivered through the Expanded Programme on Immunization. The RTS,S/AS candidate vaccine has been evaluated in multiple phase I/II studies and shown to have a favourable safety profile and to be well-tolerated in both adults and children. This paper details the design of the phase III multicentre efficacy trial of the RTS,S/AS01 malaria vaccine candidate, which is pivotal for licensure and policy decision-making. Methods The phase III trial is a randomized, controlled, multicentre, participant- and observer-blind study on-going in 11 centres associated with different malaria transmission settings in seven countries in sub-Saharan Africa. A minimum of 6,000 children in each of two age categories (6-12 weeks, 5-17 months) have been enrolled. Children were randomized 1:1:1 to one of three study groups: (1) primary vaccination with RTS,S/AS01 and booster dose of RTS,S/AS01; (2) primary vaccination with RTS,S/AS01 and a control vaccine at time of booster; (3) primary vaccination with control vaccine and a control vaccine at time of booster. Primary vaccination comprises three doses at monthly intervals; the booster dose is administered at 18 months post-primary course. Subjects will be followed to study month 32. The co-primary objectives are the evaluation of efficacy over one year post-dose 3 against clinical malaria when primary immunization is delivered at: (1) 6-12 weeks of age, with co-administration of DTPwHepB/Hib antigens and OPV; (2) 5-17 months of age. Secondary objectives include evaluation of vaccine efficacy against severe malaria, anaemia, malaria hospitalization, fatal malaria, all-cause mortality and other serious illnesses including sepsis and pneumonia. Efficacy of the vaccine against clinical malaria under different transmission settings, the evolution of efficacy over time and the potential benefit of a booster will be evaluated. In addition, the effect of RTS,S/AS01 vaccination on growth, and the safety and immunogenicity in HIV-infected and malnourished children will be assessed. Safety of the primary course of immunization and the booster dose will be documented in both age categories. Conclusions This pivotal phase III study of the RTS,S/AS01 candidate malaria vaccine in African children was designed and implemented by the Clinical Trials Partnership Committee. The study will provide efficacy and safety data to fulfil regulatory requirements, together with data on a broad range of endpoints that will facilitate the evaluation of the public health impact of the vaccine and will aid policy and implementation decisions. Trial registration Clinicaltrials.gov NCT00866619 PMID:21816029

A systematic analysis of acceptor specificity and reaction kinetics of five human α(2,3)sialyltransferases: Product inhibition studies illustrate reaction mechanism for ST3Gal-I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Rohitesh, E-mail: rohitesh.gupta@gmail.com; Matta, Khushi L.; Neelamegham, Sriram, E-mail: neel@buffalo.edu

2016-01-15

Sialyltransferases (STs) catalyze the addition of sialic acids to the non-reducing ends of glycoproteins and glycolipids. In this work, we examined the acceptor specificity of five human α(2,3)sialyltransferases, namely ST3Gal -I, -II, -III, -IV and -VI. K{sub M} values for each of these enzymes is presented using radioactivity for acceptors containing Type-I (Galβ1,3GlcNAc), Type-II (Galβ1,4GlcNAc), Type-III (Galβ1,3GalNAc) and Core-2 (Galβ1,3(GlcNAcβ1,6)GalNAc) reactive groups. Several variants of acceptors inhibited ST3Gal activity emphasizing structural role of acceptor in enzyme-catalyzed reactions. In some cases, mass spectrometry was performed for structural verification. The results demonstrate human ST3Gal-I catalysis towards Type-III and Core-2 acceptors with K{submore » M} = 5–50 μM and high V{sub Max} values. The K{sub M} for ST3Gal-I and ST3Gal-II was 100 and 30-fold lower, respectively, for Type-III compared to Type-I acceptors. Variants of Type-I and Type-II structures characterized ST3Gal-III, -IV and -VI for their catalytic specificity. This manuscript also estimates K{sub M} for human ST3Gal-VI using Type-I and Type-II substrates. Together, these findings built a platform for designing inhibitors of STs having therapeutic potential. - Highlights: • K{sub M} for five Human ST3Gals is reported towards Type-I, Type-II & Type-III acceptors. • LC-MS simultaneously quantifies CMP-Neu5Ac & Glycans in a sialylation reaction. • Efficient Core2 sialylation indicates co-operativitiy between ST3Gal-I & C2GnT1. • ST3Gal-I inhibition study proposes iso- or random-sequential bi-bi mechanism.« less

Face and construct validation of a next generation virtual reality (Gen2-VR) surgical simulator.

PubMed

Sankaranarayanan, Ganesh; Li, Baichun; Manser, Kelly; Jones, Stephanie B; Jones, Daniel B; Schwaitzberg, Steven; Cao, Caroline G L; De, Suvranu

2016-03-01

Surgical performance is affected by distractors and interruptions to surgical workflow that exist in the operating room. However, traditional surgical simulators are used to train surgeons in a skills laboratory that does not recreate these conditions. To overcome this limitation, we have developed a novel, immersive virtual reality (Gen2-VR) system to train surgeons in these environments. This study was to establish face and construct validity of our system. The study was a within-subjects design, with subjects repeating a virtual peg transfer task under three different conditions: Case I: traditional VR; Case II: Gen2-VR with no distractions and Case III: Gen2-VR with distractions and interruptions. In Case III, to simulate the effects of distractions and interruptions, music was played intermittently, the camera lens was fogged for 10 s and tools malfunctioned for 15 s at random points in time during the simulation. At the completion of the study subjects filled in a 5-point Likert scale feedback questionnaire. A total of sixteen subjects participated in this study. Friedman test showed significant difference in scores between the three conditions (p < 0.0001). Post hoc analysis using Wilcoxon signed-rank tests with Bonferroni correction further showed that all the three conditions were significantly different from each other (Case I, Case II, p < 0.0001), (Case I, Case III, p < 0.0001) and (Case II, Case III, p = 0.009). Subjects rated that fog (mean 4.18) and tool malfunction (median 4.56) significantly hindered their performance. The results showed that Gen2-VR simulator has both face and construct validity and that it can accurately and realistically present distractions and interruptions in a simulated OR, in spite of limitations of the current HMD hardware technology.

Face and Construct Validation of a Next Generation Virtual Reality (Gen2-VR©) Surgical Simulator

PubMed Central

Sankaranarayanan, Ganesh; Li, Baichun; Manser, Kelly; Jones, Stephanie B.; Jones, Daniel B.; Schwaitzberg, Steven; Cao, Caroline G. L.; De, Suvranu

2015-01-01

Introduction Surgical performance is affected by distractors and interruptions to surgical workflow that exist in the operating room. However, traditional surgical simulators are used to train surgeons in a skills lab that does not recreate these conditions. To overcome this limitation, we have developed a novel, immersive virtual reality (Gen2-VR©) system to train surgeons in these environments. This study was to establish face and construct validity of our system. Methods and Procedures The study was a within-subjects design, with subjects repeating a virtual peg transfer task under three different conditions: CASE I: traditional VR; CASE II: Gen2-VR© with no distractions and CASE III: Gen2-VR© with distractions and interruptions.. In Case III, to simulate the effects of distractions and interruptions, music was played intermittently, the camera lens was fogged for 10 seconds and tools malfunctioned for 15 seconds at random points in time during the simulation. At the completion of the study subjects filled in a 5-point Likert scale feedback questionnaire. A total of sixteen subjects participated in this study. Results Friedman test showed significant difference in scores between the three conditions (p < 0.0001). Post hoc analysis using Wilcoxon Signed Rank tests with Bonferroni correction further showed that all the three conditions were significantly different from each other (Case I, Case II, p < 0.001), (Case I, Case III, p < 0.001) and (Case II, Case III, p = 0.009). Subjects rated that fog (mean= 4.18) and tool malfunction (median = 4.56) significantly hindered their performance. Conclusion The results showed that Gen2-VR© simulator has both face and construct validity and it can accurately and realistically present distractions and interruptions in a simulated OR, in spite of limitations of the current HMD hardware technology. PMID:26092010

Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial.

PubMed

Maio, Michele; Grob, Jean-Jacques; Aamdal, Steinar; Bondarenko, Igor; Robert, Caroline; Thomas, Luc; Garbe, Claus; Chiarion-Sileni, Vanna; Testori, Alessandro; Chen, Tai-Tsang; Tschaika, Marina; Wolchok, Jedd D

2015-04-01

There is evidence from nonrandomized studies that a proportion of ipilimumab-treated patients with advanced melanoma experience long-term survival. To demonstrate a long-term survival benefit with ipilimumab, we evaluated the 5-year survival rates of patients treated in a randomized, controlled phase III trial. A milestone survival analysis was conducted to capture the 5-year survival rate of treatment-naive patients with advanced melanoma who received ipilimumab in a phase III trial. Patients were randomly assigned 1:1 to receive ipilimumab at 10 mg/kg plus dacarbazine (n = 250) or placebo plus dacarbazine (n = 252) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Eligible patients could receive maintenance ipilimumab or placebo every 12 weeks beginning at week 24. A safety analysis was conducted on patients who survived at least 5 years and continued to receive ipilimumab as maintenance therapy. The 5-year survival rate was 18.2% (95% CI, 13.6% to 23.4%) for patients treated with ipilimumab plus dacarbazine versus 8.8% (95% CI, 5.7% to 12.8%) for patients treated with placebo plus dacarbazine (P = .002). A plateau in the survival curve began at approximately 3 years. In patients who survived at least 5 years and continued to receive ipilimumab, grade 3 or 4 immune-related adverse events were observed exclusively in the skin. The additional survival benefit of ipilimumab plus dacarbazine is maintained with twice as many patients alive at 5 years compared with those who initially received placebo plus dacarbazine. These results demonstrate a durable survival benefit with ipilimumab in advanced melanoma. © 2015 by American Society of Clinical Oncology.

Five-Year Survival Rates for Treatment-Naive Patients With Advanced Melanoma Who Received Ipilimumab Plus Dacarbazine in a Phase III Trial

PubMed Central

Maio, Michele; Grob, Jean-Jacques; Aamdal, Steinar; Bondarenko, Igor; Robert, Caroline; Thomas, Luc; Garbe, Claus; Chiarion-Sileni, Vanna; Testori, Alessandro; Chen, Tai-Tsang; Tschaika, Marina; Wolchok, Jedd D.

2015-01-01

Purpose There is evidence from nonrandomized studies that a proportion of ipilimumab-treated patients with advanced melanoma experience long-term survival. To demonstrate a long-term survival benefit with ipilimumab, we evaluated the 5-year survival rates of patients treated in a randomized, controlled phase III trial. Patients and Methods A milestone survival analysis was conducted to capture the 5-year survival rate of treatment-naive patients with advanced melanoma who received ipilimumab in a phase III trial. Patients were randomly assigned 1:1 to receive ipilimumab at 10 mg/kg plus dacarbazine (n = 250) or placebo plus dacarbazine (n = 252) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Eligible patients could receive maintenance ipilimumab or placebo every 12 weeks beginning at week 24. A safety analysis was conducted on patients who survived at least 5 years and continued to receive ipilimumab as maintenance therapy. Results The 5-year survival rate was 18.2% (95% CI, 13.6% to 23.4%) for patients treated with ipilimumab plus dacarbazine versus 8.8% (95% CI, 5.7% to 12.8%) for patients treated with placebo plus dacarbazine (P = .002). A plateau in the survival curve began at approximately 3 years. In patients who survived at least 5 years and continued to receive ipilimumab, grade 3 or 4 immune-related adverse events were observed exclusively in the skin. Conclusion The additional survival benefit of ipilimumab plus dacarbazine is maintained with twice as many patients alive at 5 years compared with those who initially received placebo plus dacarbazine. These results demonstrate a durable survival benefit with ipilimumab in advanced melanoma. PMID:25713437

Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions

PubMed Central

Dobkin, Bruce H.

2014-01-01

Based on the suboptimal research pathways that finally led to multicenter randomized clinical trials (MRCTs) of treadmill training with partial body weight support and of robotic assistive devices, strategically planned successive stages are proposed for pilot studies of novel rehabilitation interventions Stage 1, consideration-of-concept studies, drawn from animal experiments, theories, and observations, delineate the experimental intervention in a small convenience sample of participants, so the results must be interpreted with caution. Stage 2, development-of-concept pilots, should optimize the components of the intervention, settle on most appropriate outcome measures, and examine dose-response effects. A well-designed study that reveals no efficacy should be published to counterweight the confirmation bias of positive trials. Stage 3, demonstration-of-concept pilots, can build out from what has been learned to test at least 15 participants in each arm, using random assignment and blinded outcome measures. A control group should receive an active practice intervention aimed at the same primary outcome. A third arm could receive a substantially larger dose of the experimental therapy or a combinational intervention. If only 1 site performed this trial, a different investigative group should aim to reproduce positive outcomes based on the optimal dose of motor training. Stage 3 studies ought to suggest an effect size of 0.4 or higher, so that approximately 50 participants in each arm will be the number required to test for efficacy in a stage 4, proof-of-concept MRCT. By developing a consensus around acceptable and necessary practices for each stage, similar to CONSORT recommendations for the publication of phase III clinical trials, better quality pilot studies may move quickly into better designed and more successful MRCTs of experimental interventions. PMID:19240197

HPTN 068: A Randomized Control Trial of a Conditional Cash Transfer to Reduce HIV Infection in Young Women in South Africa-Study Design and Baseline Results.

PubMed

Pettifor, Audrey; MacPhail, Catherine; Selin, Amanda; Gómez-Olivé, F Xavier; Rosenberg, Molly; Wagner, Ryan G; Mabuza, Wonderful; Hughes, James P; Suchindran, Chirayath; Piwowar-Manning, Estelle; Wang, Jing; Twine, Rhian; Daniel, Tamu; Andrew, Philip; Laeyendecker, Oliver; Agyei, Yaw; Tollman, Stephen; Kahn, Kathleen

2016-09-01

Young women in South Africa are at high risk for HIV infection. Cash transfers offer promise to reduce HIV risk. We present the design and baseline results from HPTN 068, a phase III, individually randomized trial to assess the effect of a conditional cash transfer on HIV acquisition among South African young women. A total of 2533 young women were randomized to receive a monthly cash transfer conditional on school attendance or to a control group. A number of individual-, partner-, household- and school-level factors were associated with HIV and HSV-2 infection. After adjusting for age, all levels were associated with an increased odds of HIV infection with partner-level factors conveying the strongest association (aOR 3.05 95 % CI 1.84-5.06). Interventions like cash transfers that address structural factors such as schooling and poverty have the potential to reduce HIV risk in young women in South Africa.

Customizing chemotherapy in non-small cell lung cancer: the promise is still unmet

PubMed Central

2015-01-01

A combination of cytotoxic agents with cis-platin remains the cornerstone of treatment for the vast majority of patients with non-small cell lung cancer (NSCLC). Molecular analysis of the primary may lead better prognostication and eventually in more accurate therapeutic approaches. Data from retrospective analysis of randomized trials as well as large patients’ series have suggested that chemotherapy may be customized upon molecular-genetic analysis of the tumor cells. The Spanish Lung Cancer Group (SLCG) in collaboration with French lung Cancer Group (FLCG) had conduct randomized, phase III, biomarkers-driven trial and supported simultaneously a randomized phase II trial in collaborating centers in China. Despite the evidence from the preclinical data and the results from the retrospective studies, the results of these trials published recently in Annals of Oncology were in favor of ‘standard approach’. The present commentary tries to give some explanation for the disappointing results, provide potential solution for the future trials and explain why the vision of customizing treatment is still alive. PMID:26629440

Arthroscopic cartilage debridement by excimer laser in chondromalacia of the knee joint. A prospective randomized clinical study.

PubMed

Raunest, J; Löhnert, J

1990-01-01

A new operative technique in arthroscopic treatment of chondromalacia using ultraviolet laser systems is introduced. The postoperative results are evaluated in a prospective and randomized clinical trial. One hundred and forty patients stage II or III chondromalacia according to Outerbridge were randomly assigned to arthroscopic operation using either laser or mechanical instruments. After a 6-month follow-up period the clinical results were compared, guided by a specially designed modification of the Lysholm scoring scale. In the short-term follow-up laser surgery gave superior results in regard to reducing pain (P less than 0.05) and leading to a lower incidence of reactive synovitis (P less than 0.01). No difference was found in respect of disability and functional impairment. Our results lead to the conclusion that arthroscopic laser application seems to be a successful procedure in the treatment of degenerative cartilage disorders, providing precise ablation of tissue without significant thermal damage to the remaining cartilage.

Does the Well-Being of Individuals with Down Syndrome and Dementia Improve When Using Life Story Books and Rummage Boxes? A Randomized Single Case Series Experiment.

PubMed

Crook, Nicola; Adams, Malcolm; Shorten, Nicola; Langdon, Peter E

2016-01-01

This study investigated whether a personalized life story book and rummage box enhanced well-being and led to changes in behaviour for people with Down syndrome (DS) who have dementia. A randomized single case series design was used with five participants who had DS and a diagnosis of dementia. Participants were invited to take part in three conditions at random (i) life story book, (ii) rummage box and (iii) no-intervention condition. The two reminiscence conditions were significantly associated with enhanced well-being as compared to the no-intervention condition. However, for one participant, the life story book was associated with significantly higher well-being, while for another participant, the rummage box was associated with significantly higher well-being, suggesting some participants may prefer one method over another. Personalized life story books and rummage boxes are associated with higher levels of well-being for people with DS and dementia. © 2015 John Wiley & Sons Ltd.

Is clarithromycin a potential treatment for cachexia in people with lung cancer? A feasibility study.

PubMed

Awan, Sarah; Crosby, Vincent; Potter, Vanessa; Hennig, Ivo; Baldwin, David; Ndlovu, Mehluli; Paradine, Sharon; Wilcock, Andrew

2017-02-01

Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250mg twice daily or placebo for eight weeks. Aspects of trial feasibility recorded included numbers eligible, approached and recruited, together with adherence and completion of treatment and assessments. Over 6 months, none of 125 patients identified fulfilled the entry criteria. The commonest reasons for ineligibility were the use of an excluded concurrent drug (45, 36%), brain metastases (22, 18%), poor performance status (21, 17%) and current chemotherapy (15, 12%). A phase III trial of clarithromycin using these entry criteria is not feasible in this setting. Other macrolides that have a lower risk of a drug-drug interaction may be more practical to pursue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A comparative study of the health record cards in primary schools of Delhi.

PubMed

Handa, Ajay; Gupta, Sanjay; Tiwari, V K

2008-11-01

A comparative study was undertaken to understand the various measures required to strengthen and improve the health record cards (HRC) of various schools that subsequently help in improving the medical examination of children. By using a multi stage stratified random sampling method, 24 schools from Delhi, eight each from three broad categories of (i) corporation schools, (ii) other government schools, (iii) private schools were included in the study. The study finding revealed that in most of the government schools the health record cards were properly developed and structured as per the recommendations of various committee, though they are always in short supply.

T-scan III system diagnostic tool for digital occlusal analysis in orthodontics - a modern approach.

PubMed

Trpevska, Vesna; Kovacevska, Gordana; Benedeti, Alberto; Jordanov, Bozidar

2014-01-01

This systematic literature review was performed to establish the mechanism, methodology, characteristics, clinical application and opportunities of the T-Scan III System as a diagnostic tool for digital occlusal analysis in different fields of dentistry, precisely in orthodontics. Searching of electronic databases, using MEDLINE and PubMed, hand searching of relevant key journals, and screening of reference lists of included studies with no language restriction was performed. Publications providing statistically examined data were included for systematic review. Twenty potentially relevant Randomized Controlled Trials (RCTs) were identified. Only ten met the inclusion criteria. The literature demonstrates that using digital occlusal analysis with T-Scan III System in orthodontics has significant advantage with regard to the capability of measuring occlusal parameters in static positions and during dynamic of the mandible. Within the scope of this systematic review, there is evidence to support that T-Scan system is rapid and accurate in identifying the distribution of the tooth contacts and it shows great promise as a clinical diagnostic screening device for occlusion and for improving the occlusion after various dental treatments. Additional clinical studies are required to advance the indication filed of this system. Importance of using digital occlusal T-Scan analysis in orthodontics deserves further investigation.

47 CFR 1.2110 - Designated entities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection... company” as defined by the Communications Act; and (iii) The applicant (or the controlling interest... office space and/or employees and/or other facilities with another concern, particularly where such...

47 CFR 1.2110 - Designated entities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection... company” as defined by the Communications Act; and (iii) The applicant (or the controlling interest... office space and/or employees and/or other facilities with another concern, particularly where such...

47 CFR 1.2110 - Designated entities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection... company” as defined by the Communications Act; and (iii) The applicant (or the controlling interest... office space and/or employees and/or other facilities with another concern, particularly where such...

49 CFR 219.4 - Recognition of a foreign railroad's workplace testing program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... policy dealing with co-worker and self-reporting of alcohol and drug abuse problems; (iii) Random drug... delivery. Room W12-140 on the ground floor of the West Building, 1200 New Jersey Avenue, SE., Washington...

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

Quasi-experimental study designs series-paper 2: complementary approaches to advancing global health knowledge.

PubMed

Geldsetzer, Pascal; Fawzi, Wafaie

2017-09-01

Quasi-experiments have been infrequently used in the health sciences. Focusing on health systems implementation research, this article details key advantages of quasi-experiments and argues that they can complement (but not replace) randomized evaluations. Specifically, it may be possible to use a quasi-experiment to study the causal effect of an intervention that cannot feasibly be randomized or that would be unethical (e.g., because the intervention has become the standard of care) to test in a randomized controlled trial (RCT). In addition, because they usually take advantage of routinely collected data, quasi-experiments may be feasible when it is too costly (either financially or in terms of the required time) to carry out a RCT - an important advantage in research on health systems, which vary widely between settings. Nonetheless, we argue that RCTs will continue to be indispensable for implementation research because i) the assumptions needed to establish causality with a quasi-experiment are often unverifiable, ii) available data frequently do not allow for a rigorous quasi-experiment, and iii) randomized designs tend to lend themselves more to informing policy makers of causal effects prior to (or during) the full-scale rollout of an intervention than quasi-experiments. Copyright © 2017 Elsevier Inc. All rights reserved.

Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.

PubMed

Heimberger, Amy B; Archer, Gary E; Crotty, Laura E; McLendon, Roger E; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

2002-01-01

Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by DCs have also been demonstrated to produce clinically significant autoimmunity. Targeting the epidermal growth factor receptor variant III (EGFRvIII), which is a mutation specific to tumor tissue, could eliminate this risk. The purpose of this study was to demonstrate that DC-based immunizations directed solely against this tumor-specific antigen, which is commonly found on tumors that originate within or metastasize to the brain, could be efficacious. C3H mice were vaccinated with DCs mixed with a keyhole limpet hemocyanin conjugate of the tumor-specific peptide, PEP-3, which spans the EGFRvIII mutation, or the random-sequence peptide, PEP-1, and were intracerebrally challenged with a syngeneic melanoma expressing a murine homologue of EGFRvIII. Systemic immunization with DCs mixed with PEP-3-keyhole limpet hemocyanin generated antigen-specific immunity. Among mice challenged with intracerebral tumors, this resulted in an approximately 600% increase in the median survival time (>300 d, P < 0.0016), relative to control values. Sixty-three percent of mice treated with DCs mixed with the tumor-specific peptide survived in the long term and 100% survived rechallenge with tumor, indicating that antitumor immunological memory was also induced. In a murine melanoma model, immunization with DCs mixed with tumor-specific peptide results in an antigen-specific immunological response that recognizes the EGFRvIII mutation, has potent antitumor efficacy against intracerebral tumors that express EGFRvIII, and results in long-lasting antitumor immunity.

Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Xie, Sharon X; Amsterdam, Jay D.

2014-01-01

Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model.

PubMed

Chang, Panpan; Weykamp, Michael; Dennahy, Isabel S; Williams, Aaron M; Bhatti, Umar F; Liu, Baoling; Nikolian, Vahagn C; Li, Yongqing; Alam, Hasan B

2018-05-01

Hemorrhage is a leading preventable cause of death. Nonselective histone deacetylase inhibitors (HDACIs), such as valproic acid (VPA), have been shown to improve outcomes in hemorrhagic shock (HS). The HDACs can be divided into four functional classes (I, IIa/IIb, III, and IV). Classes I, IIa/IIb, and III have previously been implicated in the pathophysiology of HS. This study aimed to determine which HDAC class, or classes, are responsible for the survival benefit observed with nonselective HDACIs. Survival study: Sprague-Dawley rats were subjected to lethal HS (50% hemorrhage) and randomized to the following groups (n = 8): (1) no treatment, (2) normal saline vehicle, (3) cyclodextrin vehicle, (4) MS275 (class I HDACI), (5) VPA (class I/IIa HDACI), (6) MC1568 (class IIa HDACI), (7) ACY1083 (class IIb HDACI), and (8) EX527 (class III HDACI). Survival was monitored for 24 hours. Mechanistic study: Sprague-Dawley rats were subjected to sublethal HS (40% hemorrhage) and randomized to the same groups (n = 3), excluding EX527, based on results of the survival study. Tissues were harvested at 3 hours posttreatment, and expression of phosphorylated-AKT, β-catenin, acetylated histones H3 and H4, and acetylated α-tubulin were analyzed in myocardial tissue. Survival rate was 12.5% in the untreated group, and did not improve with vehicle or MS275 treatment. EX527 improved survival to 50%, although this did not achieve statistical significance (p = 0.082). However, treatment with VPA, MC1568, and ACY1083 improved survival rates to 87.5%, 75%, and 75%, respectively (p < 0.05). The VPA-induced acetylation of both histones H3 and H4, while MC1568 and ACY1083 increased acetylation of histone H4. ACY1083 also induced acetylation of α-tubulin. All treatment groups, except MS275, increased phosphorylated-AKT, and β-catenin. Inhibition of HDAC classes IIa or IIb, but not class I, activates prosurvival pathways, which may be responsible for the improved outcomes in rodent models of HS.

A randomized, controlled, single-blind, 6-month pilot study to evaluate the efficacy of MS-Line!: a cognitive rehabilitation programme for patients with multiple sclerosis.

PubMed

Gich, Jordi; Freixanet, Jordi; García, Rafael; Vilanova, Joan Carles; Genís, David; Silva, Yolanda; Montalban, Xavier; Ramió-Torrentà, Lluís

2015-09-01

MS-Line! was created to provide an effective treatment for cognitive impairment in multiple sclerosis (MS) patients. To assess the efficacy of MS-Line!. A randomized, controlled, single-blind, 6-month pilot study. Patients were randomly assigned to an experimental group (cognitive rehabilitation with the programme) or to a control group (no cognitive rehabilitation). Randomization was stratified by cognitive impairment level. Cognitive assessment included: selective reminding test, 10/36 spatial recall test (10/36 SPART), symbol digit modalities test, paced auditory serial addition test, word list generation (WLG), FAS test, subtests of WAIS-III, Boston naming test (BNT), and trail making test (TMT). Forty-three patients (22 in the experimental group, 21 in the control group) were analyzed. Covariance analysis showed significant differences in 10/36 SPART (P=0.0002), 10/36 SPART delayed recall (P=0.0021), WLG (P=0.0123), LNS (P=0.0413), BNT (P=0.0007) and TMT-A (P=0.010) scores between groups. The study showed a significant improvement related to learning and visual memory, executive functions, attention and information processing speed, and naming ability in those patients who received cognitive rehabilitation. The results suggest that MS-Line! is effective in improving cognitive impairment in MS patients. © The Author(s), 2015.

A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis.

PubMed

Lee, Myungchul; Yoo, Juhyung; Kim, Jin Goo; Kyung, Hee-Soo; Bin, Seong-Il; Kang, Seung-Baik; Choi, Choong Hyeok; Moon, Young-Wan; Kim, Young-Mo; Han, Seong Beom; In, Yong; Choi, Chong Hyuk; Kim, Jongoh; Lee, Beom Koo; Cho, Sangsook

2017-12-01

The aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA). This study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations. After 6 weeks, the polmacoxib-placebo treatment difference was -2.5 (95% confidence interval [CI], -4.4 to -0.6; p = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, -0.9 to 2.2; p = 0.425). According to Physician's Global Assessments, more subjects were "much improved" at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo. Polmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA.

A Randomized, Multicenter, Double-blind, Phase III Study to Evaluate the Efficacy on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and Levocetirizine in Patients With Asthma and Allergic Rhinitis.

PubMed

Kim, Mi-Kyeong; Lee, Sook Young; Park, Hae-Sim; Yoon, Ho Joo; Kim, Sang-Ha; Cho, Young Joo; Yoo, Kwang-Ha; Lee, Soo-Keol; Kim, Hee-Kyoo; Park, Jung-Won; Park, Heung-Woo; Chung, Jin-Hong; Choi, Byoung Whui; Lee, Byung-Jae; Chang, Yoon-Seok; Jo, Eun-Jung; Lee, Sang-Yeub; Cho, You Sook; Jee, Young-Koo; Lee, Jong-Myung; Jung, Jina; Park, Choon-Sik

2018-06-24

The aim of this study was to evaluate the efficacy and safety of a fixed-dose combination of montelukast and levocetirizine in patients with perennial allergic rhinitis with mild to moderate asthma compared with the efficacy and safety of montelukast alone. This study was a 4-week, randomized, multicenter, double-blind, Phase III trial. After a 1-week placebo run-in period, the subjects were randomized to receive montelukast (10mg/day, n = 112) or montelukast (10 mg/day)/levocetirizine (5 mg/day) (n = 116) treatment for 4 weeks. The primary efficacy end point was mean daytime nasal symptom score. Other efficacy end points included mean nighttime nasal symptom score, mean composite symptom score, overall assessment of allergic rhinitis by both subjects and physicians, forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC, asthma control test score, and the frequency of rescue medication used during the treatment period. Of 333 patients screened for this study, 228 eligible patients were randomized to treatment. The mean (SD) age of patients was 43.32 (15.02) years, and two thirds of subjects were female (66.67%). The demographic characteristics were similar between the treatment groups. Compared with the montelukast group, the montelukast/levocetirizine group reported significant reductions in mean daytime nasal symptom score (least squares mean [SE] of combination vs montelukast, -0.98 [0.06] vs -0.81 [0.06]; P = 0.045). For all other allergic rhinitis efficacy end points, the montelukast/levocetirizine group showed greater improvement than the montelukast group. Similar results were observed in overall assessment scores and in FEV 1 , FVC, FEV 1 /FVC, and asthma control test score changes from baseline for the 2 treatment groups. Montelukast/levocetirizine was well tolerated, and the safety profile was similar to that observed in the montelukast group. The fixed-dose combination of montelukast and levocetirizine was effective and safe in treating perennial allergic rhinitis in patients with asthma compared with montelukast alone. ClinicalTrials.gov identifier: NCT02552667. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Root cementum modulates periodontal regeneration in Class III furcation defects treated by the guided tissue regeneration technique: a histometric study in dogs.

PubMed

Gonçalves, Patricia F; Gurgel, Bruno C V; Pimentel, Suzana P; Sallum, Enilson A; Sallum, Antonio W; Casati, Márcio Z; Nociti, Francisco H

2006-06-01

Because the possibility of root cementum preservation as an alternative approach for the treatment of periodontal disease has been demonstrated, this study aimed to histometrically evaluate the effect of root cementum on periodontal regeneration. Bilateral Class III furcation defects were created in dogs, and each dog was randomly assigned to receive one of the following treatments: control (group A): scaling and root planing with the removal of root cementum; or test (group B): removal of soft microbial deposits by polishing the root surface with rubber cups and polishing paste, aiming at maximum cementum preservation. Guided tissue regeneration (GTR) was applied to both groups. Four months after treatment, a superior length of new cementum (3.59 +/- 1.67 mm versus 6.20 +/- 2.26 mm; P = 0.008) and new bone (1.86 +/- 1.76 mm versus 4.62 +/- 3.01 mm; P = 0.002) and less soft tissue along the root surface (2.77 +/- 0.79 mm versus 1.10 +/- 1.48 mm; P = 0.020) was observed for group B. Additionally, group B presented a larger area of new bone (P = 0.004) and a smaller area of soft tissue (P = 0.008). Within the limits of this study, root cementum may modulate the healing pattern obtained by guided tissue regeneration in Class III furcation defects.

The clinical safety of ibrutinib in chronic lymphocytic leukemia.

PubMed

Molica, Stefano

2015-10-01

Ibrutinib , a targeted inhibitor of B-cell receptor signaling, achieved impressive clinical results for patients with chronic lymphocytic leukemia (CLL). These results allowed the approval of ibrutinib for the treatment of patients with CLL who have received at least one prior therapy and those with a 17p deletion regardless of line of therapy. Comprehensive data from either Phase I-II or randomized Phase III studies are analyzed in this article. In addition, we reviewed data on the prevalence and the clinical management of some peculiar toxicities ibrutinib related such as lymphocytosis, major bleeding and atrial fibrillation. Ibrutinib has radically changed the scenery of relapsed/refractory CLL treatment and established an important paradigm in the molecularly targeted approach of this disease. Discontinuation of ibrutinib is rarely due to adverse events related to the drug. Patients who discontinue treatment represent a challenge to the physicians because treatment options are very limited.

Probiotics in diverticular disease of the colon: an open label study.

PubMed

Lamiki, Pepu; Tsuchiya, Junji; Pathak, Surajit; Okura, Ruichi; Solimene, Umberto; Jain, Shalini; Kawakita, Shichiro; Marotta, Francesco

2010-03-01

To investigate the effectiveness and safety of a symbiotic mixture in preventing recurrence of constipation-related abdominal pain in patients with uncomplicated diverticular disease of the colon. Forty-six consecutive patients (10 men, 36 women, mean age 62.5 years, range 49 to 77 years), previously affected by symptomatic uncomplicated diverticular disease of the colon, were enrolled in a 6-month follow-up study in a prospective, randomized, open-label study. The following symptoms were assessed at entry and through follow-up by using a quantitative scale: constipation, diarrhoea and abdominal pain. After recruitment, the patients were assigned to the following treatment: SCM-III symbiotic mixture, 10 ml three times a day. The colonization of ingested Lactobacillus acidophilus 145 and Bifidobacterium spp. 420 was assessed by species-specific PCR. Forty-five patients completed the study (97%). Thirty-one patients (68%) were still symptom free after the 6th month of treatment. Treatment with SCM-III was regarded as "effective" or "very effective" in more than 78% of the patients altogether (p<0.01 vs baseline values). The microbiological study showed that, as compared to baseline values, SCM-III enabled a significant increase of the lactobacilli and bifidobacteria counting and a trend decrease of clostridia. Genomic analysis confirmed the survivability of the ingested strain as long as treatment was given. The present symbiotic mixture seems to be effective in preventing recurrence of symptomatic uncomplicated diverticular disease of the colon, especially in those patients with constipation-predominant features.

First passage time: Connecting random walks to functional responses in heterogeneous environments (Invited)

NASA Astrophysics Data System (ADS)

Lewis, M. A.; McKenzie, H.; Merrill, E.

2010-12-01

In this talk I will outline first passage time analysis for animals undertaking complex movement patterns, and will demonstrate how first passage time can be used to derive functional responses in predator prey systems. The result is a new approach to understanding type III functional responses based on a random walk model. I will extend the analysis to heterogeneous environments to assess the effects of linear features on functional responses in wolves and elk using GPS tracking data.

Randomized Prospective Study of Endoscopic Rubber Band Ligation Compared With Bipolar Coagulation for Chronically Bleeding Internal Hemorrhoids

PubMed Central

Jutabha, Rome; Jensen, Dennis M.; Chavalitdhamrong, Disaya

2013-01-01

OBJECTIVES: Our purpose was to compare the efficacy, complications, success rate, recurrence rate at 1 year, and crossovers of rubber band ligation (RBL) with those of bipolar electrocoagulation (BPEC) treatment for chronically bleeding internal hemorrhoids. METHODS: A total of 45 patients of mean age 51.5 years, who had rectal bleeding from grade II or III hemorrhoids and in whom intensive medical therapy failed, were randomized in a prospective study comparing RBL with BPEC. Treatment failure was predefined as continued bleeding, occurrence of a major complication, or failure to reduce the size of all internal hemorrhoidal segments to grade I in ≤ 3 treatments. Patients were followed up for 1 year. RESULTS: With similar patients, rectal bleeding and other symptoms were controlled with significantly fewer treatments of RBL than of BPEC (2.3±0.2 vs. 3.8±0.4, P < 0.05), and RBL had a significantly higher success rate (92% vs. 62%, P< 0.05). RBL had more cases of severe pain during treatment (8% vs. 0%, P> 0.05), but significantly fewer failures and crossovers (8% vs. 38%). Symptomatic recurrence at 1 year was 10% RBL and 15% BPEC. CONCLUSIONS: For patients with chronically bleeding grade II or III internal hemorrhoids that are unresponsive to medical therapy, safety and complication rates of banding and BPEC were similar. The success rate was significantly higher with RBL than with BPEC. Symptom recurrence rates at 1 year were similar. PMID:19513028

The effectiveness of dry-cupping in preventing post-operative nausea and vomiting by P6 acupoint stimulation: A randomized controlled trial.

PubMed

Farhadi, Khosro; Choubsaz, Mansour; Setayeshi, Khosro; Kameli, Mohammad; Bazargan-Hejazi, Shahrzad; Heidari Zadie, Zahra; Ahmadi, Alireza

2016-09-01

Postoperative nausea and vomiting (PONV) is a common complication after general anesthesia, and the prevalence ranges between 25% and 30%. The aim of this study was to determine the preventive effects of dry cupping on PONV by stimulating point P6 in the wrist. This was a randomized controlled trial conducted at the Imam Reza Hospital in Kermanshah, Iran. The final study sample included 206 patients (107 experimental and 99 controls). Inclusion criteria included the following: female sex; age>18 years; ASA Class I-II; type of surgery: laparoscopic cholecystectomy; type of anesthesia: general anesthesia. Exclusion criteria included: change in the type of surgery, that is, from laparoscopic cholecystectomy to laparotomy, and ASA-classification III or more. Interventions are as follows: pre surgery, before the induction of anesthesia, the experimental group received dry cupping on point P6 of the dominant hand's wrist with activation of intermittent negative pressure. The sham group received cupping without activation of negative pressure at the same point. Main outcome was that the visual analogue scale was used to measure the severity of PONV. The experimental group who received dry cupping had significantly lower levels of PONV severity after surgery (P < 0.001) than the control group. The differences in measure were maintained after controlling for age and ASA in regression models (P < 0.01). Traditional dry cupping delivered in an operation room setting prevented PONV in laparoscopic cholecystectomy patients.

Lanreotide autogel every 6 weeks compared with Lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a Phase III Study.

PubMed

Bajetta, Emilio; Procopio, Giuseppe; Catena, Laura; Martinetti, Antonia; De Dosso, Sara; Ricci, Sergio; Lecchi, Alberto S; Boscani, Paolo F; Iacobelli, Stefano; Carteni, Giacomo; De Braud, Filippo; Loli, Paola; Tartaglia, Andreas; Bajetta, Roberto; Ferrari, Leonardo

2006-11-15

The noninferiority of a 6-week dosing schedule of lanreotide Autogel (Lan ATG) at a dose of 120 mg compared with a 3-week dosing schedule of lanreotide microparticles (Lan MP) at a dose of 60 mg was investigated in patients with neuroendocrine tumors (NET). Patients who had sporadic, well differentiated NET with a low grade of malignancy were recruited for this open-label, Phase III, multicenter trial. Patients were randomized to receive either 3 deep subcutaneous injections of Lan ATG (120 mg, every 6 weeks) or 6 intramuscular injections of Lan MP (60 mg, every 3 weeks). Tumor markers, tumor size, and symptoms were assessed between baseline and Week 18. Success was classified as a response that ranged from disappearance to an increase <25% in tumor marker, tumor size, or symptom frequency. Sixty patients were randomized, and 46 patients completed the study. Both for tumor markers and for tumor size, Lan ATG was not inferior to Lan MP (55% and 59% of patients responded on tumor markers, respectively; 68% and 66% of patients responded on tumor size, respectively). There were too few symptomatic patients to compare carcinoid symptoms. Both treatments were tolerated well, and no safety concerns were identified. Lan ATG at a dose of 120 mg every 6 weeks was as effective for controlling NET as Lan MP at a dose of 60 mg every 3 weeks.

The effect of cassia fistula emulsion on pediatric functional constipation in comparison with mineral oil: a randomized, clinical trial

PubMed Central

2012-01-01

Background The prevalence of Pediatric Functional Constipation (FC) has been reported between 0.7% to 29.6%. This study was conducted to compare the laxative effect of cassia fistula emulsion (CFE) with mineral oil (MO) on FC. Cassia fistula is named in Traditional Iranian Medicine (TIM) as “Folus”. Materials and methods A randomized clinical trial was carried on 81 children (age range: 4–13 years) with FC, according to Rome III criteria in Amirkola Children’s Hospital, Babol, Iran. They received CFE or MO randomly for three weeks. CFE was produced according to the order of TIM references. Children were counted as improved when they exited from Rome III criteria of FC. Frequency of defecation, fecal incontinence, retentive posturing, severity of pain, consistency of stool and anal leakage of oily material were compared between the two groups and with baselines. An intent-to-treat analysis was used. Safety of drugs was assessed with the evaluation of clinical adverse effects. Results 41 children were assigned randomly to receive CFE and 40 children received MO. After three weeks of medication, 84% of children in CFE group and 50% in MO group (p = 0.002) exited from the criteria of FC, so called improved. All measurable criteria improved in both groups. The frequency of defecation in CFE group improved from 1.7 per week (before the study) to 10.6 per week (at the third week) while this parameter differed in MO group from 2 to 6.1 (p < 0.001). The severity of pain during defecation and consistency of stool improved significantly better in CFE group than MO group (p < 0.05), but there were not any significant differences between the two groups in fecal incontinence and retentive posturing. Anal leakage of oily material occurred as an important complication in MO group while the children in CFE group did not complaint it. Drug’s compliances were not significantly different in the two groups. CFE and MO did not cause clinically significant side effects. Conclusions CFE was most effective than MO in the 3-week treatment of children with FC. PMID:23351337

Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

PubMed

Soiffer, Robert J; Kim, Haesook T; McGuirk, Joseph; Horwitz, Mitchell E; Johnston, Laura; Patnaik, Mrinal M; Rybka, Witold; Artz, Andrew; Porter, David L; Shea, Thomas C; Boyer, Michael W; Maziarz, Richard T; Shaughnessy, Paul J; Gergis, Usama; Safah, Hana; Reshef, Ran; DiPersio, John F; Stiff, Patrick J; Vusirikala, Madhuri; Szer, Jeff; Holter, Jennifer; Levine, James D; Martin, Paul J; Pidala, Joseph A; Lewis, Ian D; Ho, Vincent T; Alyea, Edwin P; Ritz, Jerome; Glavin, Frank; Westervelt, Peter; Jagasia, Madan H; Chen, Yi-Bin

2017-12-20

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Final efficacy and updated safety results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer.

PubMed

Bell, R; Brown, J; Parmar, M; Toi, M; Suter, T; Steger, G G; Pivot, X; Mackey, J; Jackisch, C; Dent, R; Hall, P; Xu, N; Morales, L; Provencher, L; Hegg, R; Vanlemmens, L; Kirsch, A; Schneeweiss, A; Masuda, N; Overkamp, F; Cameron, D

2017-04-01

The purpose of this analysis was to assess the long-term impact of adding bevacizumab to adjuvant chemotherapy for early triple-negative breast cancer (TNBC). Patients eligible for the open-label randomized phase III BEATRICE trial had centrally confirmed triple-negative operable primary invasive breast cancer (pT1a-pT3). Investigators selected anthracycline- and/or taxane-based chemotherapy for each patient. After definitive surgery, patients were randomized 1:1 to receive ≥4 cycles of chemotherapy alone or with 1 year of bevacizumab (5 mg/kg/week equivalent). Stratification factors were nodal status, selected chemotherapy, hormone receptor status, and type of surgery. The primary end point was invasive disease-free survival (IDFS; previously reported). Secondary outcome measures included overall survival (OS) and safety. After 56 months' median follow-up, 293 of 2591 randomized patients had died. There was no statistically significant difference in OS between treatment arms in either the total population (hazard ratio 0.93, 95% confidence interval [CI] 0.74-1.17; P = 0.52) or pre-specified subgroups. The 5-year OS rate was 88% (95% CI 86-90%) in both treatment arms. Updated IDFS results were consistent with the primary IDFS analysis. Five-year IDFS rates were 77% (95% CI 75-79%) with chemotherapy alone versus 80% (95% CI 77-82%) with bevacizumab. From 18 months after first study dose to study end, new grade ≥3 adverse events occurred in 4.6% and 4.5% of patients in the two arms, respectively. Final OS results showed no significant benefit from bevacizumab therapy for early TNBC. Late-onset toxicities were rare in both groups. Five-year OS and IDFS rates suggest that the prognosis for patients with TNBC is better than previously thought. NCT00528567. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases.

PubMed

Hughes, Marybeth S; Zager, Jonathan; Faries, Mark; Alexander, H Richard; Royal, Richard E; Wood, Bradford; Choi, Junsung; McCluskey, Kevin; Whitman, Eric; Agarwala, Sanjiv; Siskin, Gary; Nutting, Charles; Toomey, Mary Ann; Webb, Carole; Beresnev, Tatiana; Pingpank, James F

2016-04-01

There is no consensus for the treatment of melanoma metastatic to the liver. Percutaneous hepatic perfusion with melphalan (PHP-Mel) is a method of delivering regional chemotherapy selectively to the liver. In this study, we report the results of a multicenter, randomized controlled trial comparing PHP-Mel with best alternative care (BAC) for patients with ocular or cutaneous melanoma metastatic to the liver. A total of 93 patients were randomized to PHP-Mel (n = 44) or BAC (n = 49). On the PHP-Mel arm, melphalan was delivered via the hepatic artery, and the hepatic effluent captured and filtered extracorporeally prior to return to the systemic circulation via a venovenous bypass circuit. PHP-Mel was repeatable every 4-8 weeks. The primary endpoint was hepatic progression-free survival (hPFS), and secondary endpoints included overall PFS (oPFS), overall survival (OS), hepatic objective response (hOR), and safety. hPFS was 7.0 months for PHP-Mel and 1.6 months for BAC (p < 0.0001), while oPFS was 5.4 months for PHP-Mel and 1.6 months for BAC (p < 0.0001). Median OS was not significantly different (PHP-Mel 10.6 months vs. BAC 10.0 months), likely due to crossover to PHP-Mel treatment (57.1 %) from the BAC arm, and the hOR was 36.4 % for PHP-Mel and 2.0 % for BAC (p < 0.001). The majority of adverse events were related to bone marrow suppression. Four deaths were attributed to PHP-Mel, three in the primary PHP-Mel group, and one post-crossover to PHP-Mel from BAC. This randomized, phase III study demonstrated the efficacy of the PHP-Mel procedure. hPFS, oPFS, and hOR were significantly improved with PHP-Mel. PHP with melphalan should provide a new treatment option for unresectable metastatic melanoma in the liver.

Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis.

PubMed

Tomasello, Gianluca; Barni, Sandro; Turati, Luca; Ghidini, Michele; Pezzica, Ezio; Passalacqua, Rodolfo; Petrelli, Fausto

2018-02-15

CDX2 is a homeobox gene encoding transcriptional factors for intestinal organogenesis and represents a specific marker of colorectal adenocarcinoma (CRC) differentiation. We have evaluated if CDX2 expression is associated with better overall and disease-free survival (OS and DFS) in patients with CRC. PubMed, SCOPUS, EMBASE, The Cochrane Library, and Web of Science (from inception to July 2017) were systematically reviewed for relevant studies on adult patients with CRC where OS and DFS were calculated according to CDX2 expression in uni- or multivariate analysis were included. Hazard ratio (HR) for mortality and/or disease progression was calculated. The search produced 16 studies suitable for inclusion (6291 individual patients). The meta-analysis showed a reduced risk of death for patients with CDX2-positive CRC in 14 studies (HR, 0.5; 95% confidence interval [CI], 0.38-0.66; P < .001 according to random effect model). In 6 studies where only DFS data was available, CDX2 expression led to a 52% lower risk of relapse or death (HR, 0.48; 95% CI, 0.39-0.59; P < .001 according to random effect model). The results did not change as a function of ethnicity, type of study, CDX2 detection modality, or stage. Interestingly, in stages II to III, CDX2 expression was associated with a 70% lower risk of death (HR, 0.3; 95% CI, 0.12-0.77; P = .01). CDX2 expression confirms to be a strong prognostic factor in stage II and III CRC. In this setting, along with other clinical and pathologic factors, the lack of expression of CDX2 may be considered an important variable when deciding for adjuvant chemotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Contemporary clinical trials in ventricular tachycardia and fibrillation: implications of ESVEM, CASCADE, and CASH for clinical management.

PubMed

Anderson, J L

1995-10-01

Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Holter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N=486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I( conduction slowing) effects, even when guided by EPS or HM.

Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability

PubMed Central

Greenbury, Sam F.; Schaper, Steffen; Ahnert, Sebastian E.; Louis, Ard A.

2016-01-01

Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps—a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure—to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so increase evolvability. PMID:26937652

A randomized phase II/III study of adverse events between sequential (SEQ) versus simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma; preliminary result on acute adverse events.

PubMed

Songthong, Anussara P; Kannarunimit, Danita; Chakkabat, Chakkapong; Lertbutsayanukul, Chawalit

2015-08-08

To investigate acute and late toxicities comparing sequential (SEQ-IMRT) versus simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) in nasopharyngeal carcinoma (NPC) patients. Newly diagnosed stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT, with or without chemotherapy. SEQ-IMRT consisted of two sequential radiation treatment plans: 2 Gy x 25 fractions to low-risk planning target volume (PTV-LR) followed by 2 Gy x 10 fractions to high-risk planning target volume (PTV-HR). In contrast, SIB-IMRT consisted of only one treatment plan: 2.12 Gy and 1.7 Gy x 33 fractions to PTV-HR and PTV-LR, respectively. Toxicities were evaluated according to CTCAE version 4.0. Between October 2010 and November 2013, 122 eligible patients were randomized between SEQ-IMRT (54 patients) and SIB-IMRT (68 patients). With median follow-up time of 16.8 months, there was no significant difference in toxicities between the two IMRT techniques. During chemoradiation, the most common grade 3-5 acute toxicities were mucositis (15.4% vs 13.6%, SEQ vs SIB, p = 0.788) followed by dysphagia (9.6% vs 9.1%, p = 1.000) and xerostomia (9.6% vs 7.6%, p = 0.748). During the adjuvant chemotherapy period, 25.6% and 32.7% experienced grade 3 weight loss in SEQ-IMRT and SIB-IMRT (p = 0.459). One-year overall survival (OS) and progression-free survival (PFS) were 95.8% and 95.5% in SEQ-IMRT and 98% and 90.2% in SIB-IMRT, respectively (p = 0.472 for OS and 0.069 for PFS). This randomized, phase II/III trial comparing SIB-IMRT versus SEQ-IMRT in NPC showed no statistically significant difference between both IMRT techniques in terms of acute adverse events. Short-term tumor control and survival outcome were promising.

49 CFR 382.401 - Retention of records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... substances collection process (except calibration of evidential breath testing devices). (3) One year... record is required to be prepared, it must be maintained. (1) Records related to the collection process: (i) Collection logbooks, if used; (ii) Documents relating to the random selection process; (iii...

47 CFR 1.227 - Consolidations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... application. (ii) Domestic public fixed and public mobile. See Rule § 21.31 of this chapter for the... as to amendments of applications. (iii) Public coast stations (Maritime mobile service). See... issues, or (2) Any applications which present conflicting claims, except where a random selection process...

Upper Grades Ideas.

ERIC Educational Resources Information Center

Thornburg, David; Beane, Pam

1983-01-01

Presents programs for creating animated characters (Atari), random sentences (Logo), and making a triangle (TRS-80 Level III Basic), and suggestions for creative writing and comparison shopping for computers/software. Also includes "Modems for Micros: Your Computer Can Talk on the Phone" (Bill Chalgren) on telecommunications capabilities of…

Rotigotine transdermal system and evaluation of pain in patients with Parkinson’s disease: a post hoc analysis of the RECOVER study

PubMed Central

2014-01-01

Background Pain is a troublesome non-motor symptom of Parkinson’s disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system. Improvements were also reported on a Likert pain scale (measuring any type of pain). This post hoc analysis of RECOVER further evaluates the effect of rotigotine on pain, and whether improvements in pain may be attributable to benefits in motor function or sleep disturbance. Methods PD patients with unsatisfactory early-morning motor impairment were randomized to optimal-dose (up to 16 mg/24 h) rotigotine or placebo, maintained for 4 weeks. Pain was assessed in the early-morning using an 11-point Likert pain scale (rated average severity of pain (of any type) over the preceding 12 hours from 0 [no pain] to 10 [worst pain ever experienced]). Post hoc analyses for patients reporting ‘any’ pain (pain score ≥1) at baseline, and subgroups reporting ‘mild’ (score 1–3), and ‘moderate-to-severe’ pain (score ≥4) were performed. Likert pain scale change from baseline in rotigotine-treated patients was further analyzed based on a UPDRS III/PDSS-2 responder analysis (a responder defined as showing a ≥30% reduction in early morning UPDRS III total score or PDSS-2 total score). As post hoc analyses, all p values presented are exploratory. Results Of 267 patients with Likert pain data (178 rotigotine, 89 placebo), 187 (70%) reported ‘any’ pain; of these 87 (33%) reported ‘mild’, and 100 (37%) ‘moderate-to-severe’ pain. Change from baseline pain scores decreased with rotigotine compared with placebo in patients with ‘any’ pain (-0.88 [95% CI: -1.56, -0.19], p = 0.013), and in the subgroup with ‘moderate-to-severe’ pain (-1.38 [-2.44, -0.31], p = 0.012). UPDRS III or PDSS-2 responders showed greater improvement in pain than non-responders. Conclusions The results from this post hoc analysis of the RECOVER study suggest that pain was improved in patients with PD treated with rotigotine; this may be partly attributable to benefits in motor function and sleep disturbances. Prospective studies are warranted to investigate this potential benefit and the clinical relevance of these findings. PMID:24602411

From Clinical Trials to the Front Line: Vinflunine for Treatment of Urothelial Cell Carcinoma at the National Cancer Institute of Naples

PubMed Central

Facchini, Gaetano; Della Pepa, Chiara; Cavaliere, Carla; Cecere, Sabrina C.; Di Napoli, Marilena; D'Aniello, Carmine; Crispo, Anna; Iovane, Gelsomina; Maiolino, Piera; Tramontano, Teresa; Piscitelli, Raffaele; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Sorrentino, Domenico; Perdonà, Sisto; Pignata, Sandro

2016-01-01

Background: The efficacy of Vinflunine, after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract, TCCU, has been demonstrated in an international, randomized, phase III trial comparing Vinflunine plus Best Supportive Care, BSC, with BSC alone. On the basis of that study vinflunine has been approved by the European Medicine Association, EMA, for treatment of TCCU patients after failure of a platinum treatment. However, since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring, “real life” experiences are very helpful to verify the efficacy of a new therapy. Methods: This was a spontaneous, observational, retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center, data about demographics, disease characteristics, and previous treatments were collected and outcome and toxicities of vinflunine were analyzed. Results: 41 of 43 patients were eligible for RR analysis, the Overall RR was 12%, the Disease Control Rate was 29%; when including only patients treated in II line the DCR rose to 33%; the median PFS and the median OS were 2.2 and 6.9 months, respectively. Conclusion: Our findings were consistent with the outcome data emerged in the phase III randomized trial and in the other observational studies conducted all around Europe in the last 2–3 years. This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug. PMID:27199753

Effectiveness and safety of acupuncture in the treatment of Parkinson's disease: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Noh, Hyeonseok; Kwon, Seungwon; Cho, Seung-Yeon; Jung, Woo-Sang; Moon, Sang-Kwan; Park, Jung-Mi; Ko, Chang-Nam; Park, Seong-Uk

2017-10-01

This study aimed to examine the effectiveness and safety of acupuncture in the treatment of Parkinson's disease (PD). English, Chinese, and Korean electronic databases were searched up to June 2016. Randomized controlled trials (RCTs) were eligible. The methodological quality was assessed using Cochrane's risk of bias tool. Meta-analysis was performed using RevMan 5.3. In total, 42 studies involving 2625 participants were systematically reviewed. Participants treated using combined acupuncture and conventional medication (CM) showed significant improvements in total Unified PD Rating Scale (UPDRS), UPDRS I, UPDRS II, UPDRS III, and the Webster scale compared to those treated using CM alone. The combination of electroacupuncture and CM was significantly superior to CM alone in total UPDRS, UPDRS I, UPDRS II, and UPDRS IV. Similarly, the combination of scalp electroacupuncture, acupuncture, and CM was significantly more effective than CM alone in total UPDRS. However, our meta-analysis showed that the combination of electroacupuncture and CM was not significantly more effective than CM alone in UPDRS III, the Webster, and the Tension Assessment Scale. The results also failed to show that acupuncture was significantly more effective than placebo acupuncture in total UPDRS. Overall, the methodological quality of the RCTs was low. No serious adverse events were reported. We found that acupuncture might be a safe and useful adjunctive treatment for patients with PD. However, because of methodological flaws in the included studies, conclusive evidence is still lacking. More rigorous and well-designed placebo-controlled trials should be conducted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of some cultural experimental methods to study the effects of antibiotics on microbial activities in a soil: An incubation study

PubMed Central

Molaei, Ali; Haghnia, Gholamhosain; Astaraei, Alireza; Rasouli-Sadaghiani, MirHassan; Teresa Ceccherini, Maria; Datta, Rahul

2017-01-01

Oxytetracycline (OTC) and sulfamethoxazole (SMX) are two of most widely used antibiotics in livestock and poultry industry. After consumption of antibiotics, a major portion of these compounds is excreted through the feces and urine of animals. Land application of antibiotic-treated animal wastes has caused increasing concern about their adverse effects on ecosystem health. In this regard, inconsistent results have been reported regarding the effects of antibiotics on soil microbial activities. This study was conducted based on the completely randomized design to the measure microbial biomass carbon, cumulative respiration and iron (III) reduction bioassays. Concentrations of OTC and SMX including 0, 1, 10, 25, 50, and 100 mg/kg were spiked in triplicate to a sandy loam soil and incubated for 21 days at 25°C. Results showed that the effects of OTC and SMX antibiotics on cumulative respiration and microbial biomass carbon were different. SMX antibiotic significantly affected soil microbial biomass carbon and cumulative respiration at different treatments compared to control with increasing incubation time. OTC antibiotic, on the other hand, negatively affected cumulative respiration compared to control treatment throughout the incubation period. Although OTC antibiotic positively affected microbial biomass carbon at day one of incubation, there was no clear trend in microbial biomass carbon between different treatments of this antibiotic after that time period. Nevertheless, sulfamethoxazole and oxytetracycline antibiotics had similar effects on iron (III) reduction such that they considerably affected iron (III) reduction at 1 and 10 mg/kg, and iron (III) reduction was completely inhibited at concentrations above 10 mg/kg. Hence, according to our results, microbial biomass carbon and cumulative respiration experiments are not able alone to exhibit the effect of antibiotics on soil microbial activity, but combination of these two experiments with iron (III) reduction test could well display the effects of sulfamethoxazole (SMX) and oxytetracycline (OTC) antibiotics on soil biochemical activities. PMID:28683144

Sexually transmitted agents and cervical neoplasia in Colombia and Spain.

PubMed

de Sanjosé, S; Muñoz, N; Bosch, F X; Reimann, K; Pedersen, N S; Orfila, J; Ascunce, N; González, L C; Tafur, L; Gili, M

1994-02-01

Case-control studies of cervical intra-epithelial neoplasia grade III (CIN III) and of invasive cervical cancer were carried out in Spain and Colombia to assess the relationship between cervical cancer and 6 common sexually transmitted agents (STAs). The CIN-III studies included 525 cases and 512 controls matched for age and for the place of recruitment; the invasive-cancer studies included 373 histologically confirmed cases of squamous-cell carcinoma and 387 age-stratified controls selected randomly from the populations that generated the cases. Antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex virus type II (HSV-2) and cytomegalovirus (CMV) were tested in 88% of the women. Cervical scrapes were examined for HPV DNA in 63% of the women using a polymerase-chain-reaction assay (PCR). Among controls, the highest antibody prevalence was to CMV (96.5%), followed by HSV-2 (31.4%) and C. trachomatis (23.3%). For all STAs, the sero-prevalence was markedly higher in Colombia than in Spain both for cases and for controls. After adjustment for the presence of HPV DNA, C. trachomatis was the only STA associated with CIN III in both countries; Spain and Colombia. In both countries, the risk of CIN III increased with increasing of C. trachomatis antibody titers. Among Spanish women, an increase in risk of invasive carcinoma was found for those with antibodies to N. gonorrhoeae; those with antibodies to HSV-2 and those with antibodies to C. trachomatis. These associations were present only in HPV-DNA-negative women. Among HPV-DNA-positive women, none of the STAs considered were associated with cervical neoplasia. Our findings could be interpreted as indicating that past infections with HSV-2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, we cannot exclude that these STAs are also of separate etiological significance.

Endovascular Therapy is Effective and Safe for Patients with Severe Ischemic Stroke: Pooled Analysis of IMS III and MR CLEAN Data

PubMed Central

Broderick, Joseph P.; Berkhemer, Olvert A.; Palesch, Yuko Y.; Dippel, Diederik W.J.; Foster, Lydia D.; Roos, Yvo B.W.E.M.; van der Lugt, Aad; Tomsick, Thomas A.; Majoie, Charles B.L.M.; van Zwam, Wim H.; Demchuk, Andrew M.; van Oostenbrugge, Robert J.; Khatri, Pooja; Lingsma, Hester F.; Hill, Michael D.; Roozenbeek, Bob; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig S.; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Simpson, Kit

2015-01-01

Background and Purpose We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (NIHSS ≥20) following a pre-specified analysis plan. Methods The pooled analysis of the IMS III and MR CLEAN trial included participants with an NIHSS ≥20 prior to intravenous (IV) t-PA treatment (IMS III) or randomization (MR CLEAN) who were treated with IV t-PA ≤ 3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy following IV t-PA would have improved 90-day outcome (distribution of modified Rankin scale [mRS] scores), as compared to those who received IV t-PA alone. Results Among 342 participants in the pooled analysis (194 from IMS III, 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared to the IV t-PA group (adjusted odds ratio [aOR] 1.78; 95% confidence interval [CI] 1.20-2.66). In the logistic regression model of the dichotomous outcome (mRS 0-2, or ‘functional independence’), the endovascular group had superior outcomes (aOR 1.97; 95% CI 1.09-3.56). Functional independence (mRS ≤2) at 90 days was 25% in the endovascular group as compared to 14% in the IV t-PA group. Conclusions Endovascular therapy following IV t-PA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. PMID:26486865

Microleakage in conservative cavities varying the preparation method and surface treatment

PubMed Central

ATOUI, Juliana Abdallah; CHINELATTI, Michelle Alexandra; PALMA-DIBB, Regina Guenka; CORONA, Silmara Aparecida Milori

2010-01-01

Objective To assess microleakage in conservative class V cavities prepared with aluminum-oxide air abrasion or turbine and restored with self-etching or etch-and-rinse adhesive systems. Material and Methods Forty premolars were randomly assigned to 4 groups (I and II: air abrasion; III and IV: turbine) and class V cavities were prepared on the buccal surfaces. Conditioning approaches were: groups I/III - 37% phosphoric acid; groups II/IV -self-priming etchant (Tyrian-SPe). Cavities were restored with One Step Plus/Filtek Z250. After finishing, specimens were thermocycled, immersed in 50% silver nitrate, and serially sectioned. Microleakage at the occlusal and cervical interfaces was measured in mm and calculated by a software. Data were subjected to ANOVA and Tukey’s test (α=0.05). Results Forty premolars were randomly assigned to 4 groups (I and II: air abrasion; III and IV: turbine) and class V cavities were prepared on the buccal surfaces. Conditioning approaches were: groups I/III - 37% phosphoric acid; groups II/IV -self-priming etchant (Tyrian-SPe). Cavities were restored with One Step Plus/Filtek Z250. After finishing, specimens were thermocycled, immersed in 50% silver nitrate, and serially sectioned. Microleakage at the occlusal and cervical interfaces was measured in mm and calculated by a software. Data were subjected to ANOVA and Tukey’s test (α=0.05). Conclusion Marginal seal of cavities prepared with aluminum-oxide air abrasion was different from that of conventionally prepared cavities, and the etch-and-rinse system promoted higher marginal seal at both enamel and dentin margins. PMID:20835580

Surgical versus conservative management of Type III acromioclavicular dislocation: a systematic review.

PubMed

Longo, Umile Giuseppe; Ciuffreda, Mauro; Rizzello, Giacomo; Mannering, Nicholas; Maffulli, Nicola; Denaro, Vincenzo

2017-06-01

The management of Type III acromioclavicular (AC) dislocations is still controversial. We wished to compare the rate of recurrence and outcome scores of operative versus non-operative treatment of patients with Type III AC dislocations. A systematic review of the literature was performed by applying the PRISMA guidelines according to the PRISMA checklist and algorithm. A search in Medline, PubMed, Cochrane and CINAHL was performed using combinations of the following keywords: 'dislocation', 'Rockwood', 'type three', 'treatment', 'acromioclavicular' and 'joint'. Fourteen studies were included, evaluating 646 shoulders. The rate of recurrence in the surgical group was 14%. No statistical significant differences were found between conservative and surgical approaches in terms of postoperative osteoarthritis and persistence of pain, although persistence of pain seemed to occur less frequently in patients undergoing a surgical treatment. Persistence of pain seemed to occur less frequently in patients undergoing surgery. Persistence of pain seems to occur less frequently in patients treated surgically for a Type III AC dislocation. There is insufficient evidence to establish the effects of surgical versus conservative treatment on functional outcome of patients with AC dislocation. High-quality randomized controlled clinical trials are needed to establish whether there is a difference in functional outcome. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Physiological alteration, quality of anesthesia and economy of isoflurane in domestic chickens (Gallus domesticus).

PubMed

Deori, Parag; Sarma, Kushal Konwar; Nath, Parsha Jyoti; Singh, Chandan Kumar; Nath, Rita

2017-05-01

Aim of the study was to evaluate the effect of isoflurane anesthesia on physiological parameters, assessment of anesthetic qualities, and economy of use of isoflurane in domestic chickens ( Gallus domesticus ). In this study, 18 apparently healthy adult domestic chickens were selected randomly and divided into three groups. The birds were anesthetized by masked induction with isoflurane at a dose rate of 3.5%, 4%, and 5% and were maintained with 1.5%, 2%, and 2.5% isoflurane with oxygen by endotracheal intubation in Groups I, II, and III, respectively. Physiological parameters, viz., cloacal temperature, heart rate, and respiration rate were recorded at 0, 5, 10, 20, 30, 40, 50, and 60 min. The quality of anesthesia was assessed on the basis of induction time, induction behavior, quality of sedation, production of analgesia, degree of muscle relaxation, palpebral reflex, recovery time, and recovery behavior. The economy of anesthesia was calculated in terms of quantity of isoflurane utilized during 60 min of study. Statistical analysis was performed by analysis of variance, Duncan's multiple range tests. There was significant decrease (p<0.01) in physiological parameters such as in cloacal temperature, heart rate and respiration rate in the birds of all the groups from 0 to 60 min. The induction time was 5.83±0.33, 2.37±0.18, and 0.87±0.15 min, respectively, in Groups I, II, and III. Induction behavior was smooth in Group III, whereas mildly stormy in Group II and I. Quality of sedation was excellent in Group III, better in Group II as compared to Group I. Analgesia was moderate in Group III whereas poor in Group II and I. Degree of muscle relaxation was excellent in Group III, whereas good in Group I and II. Palpebral reflexes were absent in all the groups. Recovery time was 15.33±0.84, 18.83±0.94, and 26.50±0.85 in Groups I, II, and III respectively. Recovery behavior was smooth in birds of all the groups. The cost of the anesthesia was 158.22±1.04, 194.27±0.66, and 236.84±0.60 Indian National Rupee in Groups I, II, and III, respectively. Quantity of anesthesia utilized in each group was 7.62±0.05, 9.35±0.03, and 11.41±0.03 ml in Groups I, II, and III, respectively. The use of isoflurane at different concentration produces different level of physiological changes, quality of anesthesia and economy without causing any deleterious effect on the birds. The physiological parameters observed in this study can serve as reference values for the wild and endangered birds.

Spin dynamics of random Ising chain in coexisting transverse and longitudinal magnetic fields

NASA Astrophysics Data System (ADS)

Liu, Zhong-Qiang; Jiang, Su-Rong; Kong, Xiang-Mu; Xu, Yu-Liang

2017-05-01

The dynamics of the random Ising spin chain in coexisting transverse and longitudinal magnetic fields is studied by the recursion method. Both the spin autocorrelation function and its spectral density are investigated by numerical calculations. It is found that system's dynamical behaviors depend on the deviation σJ of the random exchange coupling between nearest-neighbor spins and the ratio rlt of the longitudinal and the transverse fields: (i) For rlt = 0, the system undergoes two crossovers from N independent spins precessing about the transverse magnetic field to a collective-mode behavior, and then to a central-peak behavior as σJ increases. (ii) For rlt ≠ 0, the system may exhibit a coexistence behavior of a collective-mode one and a central-peak one. When σJ is small (or large enough), system undergoes a crossover from a coexistence behavior (or a disordered behavior) to a central-peak behavior as rlt increases. (iii) Increasing σJ depresses effects of both the transverse and the longitudinal magnetic fields. (iv) Quantum random Ising chain in coexisting magnetic fields may exhibit under-damping and critical-damping characteristics simultaneously. These results indicate that changing the external magnetic fields may control and manipulate the dynamics of the random Ising chain.

A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings.

PubMed

Mix, Joseph A; Crews, W David

2002-08-01

There appears to be an absence of large-scaled clinical trials that have examined the efficacy of Ginkgo biloba extract on the neuropsychological functioning of cognitively intact older adults. The importance of such clinical research appears paramount in light of the plethora of products containing Ginkgo biloba that are currently being widely marketed to predominantly cognitively intact adults with claims of enhanced cognitive performances. The purpose of this research was to conduct the first known, large-scaled clinical trial of the efficacy of Ginkgo biloba extract (EGb 761) on the neuropsychological functioning of cognitively intact older adults. Two hundred and sixty-two community-dwelling volunteers (both male and female) 60 years of age and older, who reported no history of dementia or significant neurocognitive impairments and obtained Mini-Mental State Examination total scores of at least 26, were examined via a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel-group, clinical trial. Participants were randomly assigned to receive either Ginkgo biloba extract EGb 761(n = 131; 180 mg/day) or placebo (n = 131) for 6 weeks. Efficacy measures consisted of participants' raw change in performance scores from pretreatment baseline to those obtained just prior to termination of treatment on the following standardized neuropsychological measures: Selective Reminding Test (SRT), Wechsler Adult Intelligence Scale-III Block Design (WAIS-III BD) and Digit Symbol-Coding (WAIS-III DS) subtests, and the Wechsler Memory Scale-III Faces I (WMS-III FI) and Faces II (WMS-III FII) subtests. A subjective Follow-up Self-report Questionnaire was also administered to participants just prior to termination of the treatment phase. Analyses of covariance indicated that cognitively intact participants who received 180 mg of EGb 761 daily for 6 weeks exhibited significantly more improvement on SRT tasks involving delayed (30 min) free recall (p < 0.04) and recognition (p < 0.01) of noncontextual, auditory-verbal material, compared with the placebo controls. The EGb 761 group also demonstrated significantly greater improvement on the WMS-III FII subtest assessing delayed (30 min) recognition (p < 0.025) of visual material (i.e. human faces), compared with the placebo group. However, based on the significant difference (p < 0.03) found between the two groups' pretreatment baseline scores on the WMS-III FII, this result should be interpreted with caution. An examination of the participants' subjective ratings of their overall abilities to remember by treatment end on the Follow-up Self-report Questionnaire also revealed that significantly more (p = 0.05) older adults in the EGb 761 group rated their overall abilities to remember by treatment end as 'improved' compared with the placebo controls. Overall, the results from both objective, standardized, neuropsychological tests and a subjective, follow-up self-report questionnaire provided complementary evidence of the potential efficacy of Ginkgo biloba EGb 761 in enhancing certain neuropsychological/memory processes of cognitively intact older adults, 60 years of age and over. Copyright 2002 John Wiley & Sons, Ltd.

Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study

PubMed Central

Li, Jing; Kang, Jian; Wang, Changzheng; Yang, Jing; Wang, Linda; Kottakis, Ioannis; Humphries, Michael

2016-01-01

Purpose Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. Methods This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). Results A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; P<0.001) and ACQ (49.5% vs 35.5%; LSM=-0.51 vs -0.34; P=0.002) scores vs placebo. Total and nighttime symptom scores reduced significantly with omalizumab vs placebo (LSM-TD=-0.21, P=0.048 and -0.12, P=0.011, respectively). Although the study was not powered to study differences in exacerbation rates (P=0.097), exacerbations in winter months were less frequent in the omalizumab vs placebo group (2 vs 21). Adverse event and severe adverse event rates were comparable between omalizumab and placebo. Conclusions Omalizumab improves lung function, quality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile. PMID:27126725

Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study.

PubMed

Li, Jing; Kang, Jian; Wang, Changzheng; Yang, Jing; Wang, Linda; Kottakis, Ioannis; Humphries, Michael; Zhong, Nanshan

2016-07-01

Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; P<0.001) and ACQ (49.5% vs 35.5%; LSM=-0.51 vs -0.34; P=0.002) scores vs placebo. Total and nighttime symptom scores reduced significantly with omalizumab vs placebo (LSM-TD=-0.21, P=0.048 and -0.12, P=0.011, respectively). Although the study was not powered to study differences in exacerbation rates (P=0.097), exacerbations in winter months were less frequent in the omalizumab vs placebo group (2 vs 21). Adverse event and severe adverse event rates were comparable between omalizumab and placebo. Omalizumab improves lung function, quality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile.

Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha (IFN-alpha) in metastatic melanoma.

PubMed

Young, A M; Marsden, J; Goodman, A; Burton, A; Dunn, J A

2001-01-01

Dacarbazine (DTIC) has been the mainstay of chemotherapy for metastatic melanoma for over two decades, but only 15%-20% of patients respond and benefit is usually transient. Randomized studies combining DTIC with interferon-alpha (IFN-alpha) in advanced disease have so far been inconclusive in terms of response and survival. We report a randomized prospective pilot Phase III trial of DTIC +IFN-alpha in patients with metastatic melanoma. The primary endpoint was death. A total of 61 patients were randomized between April 1995 and April 1998. Differences in survival between groups were assessed using log-rank analysis. Quality of life was measured using the European Organization for Research on Treatment of Cancer QLQ C30 (+3) questionnaire. Fifty-seven patients died during the study. The median survival for patients receiving DTIC was 7.2 months (95% confidence interval (CI) 4.4-9.0); it was 4.8 months for DTIC + IFN-alpha (95% CI 2.0-8.0). There was no significant difference in survival between the two treatment arms (chi2 unadjusted = 0.15, P = 0.70; chi2 adjusted = 0.01, P = 0.91). The 6-month survival of those patients randomized to DTIC alone was 58% compared with 40% for those patients randomized to DTIC + IFN-alpha. There were no differences in quality of life between treatment groups. This study failed to demonstrate a survival benefit for patients receiving IFN-alpha in combination with DTIC. These results are inconclusive primarily owing to the small size of the trial. A meta-analysis is required to determine whether there is a role for the addition of IFN-alpha to DTIC in the treatment of this disease.

Quality of Life Analysis of a Radiation Dose-Escalation Study of Patients With Non-Small-Cell Lung Cancer: A Secondary Analysis of the Radiation Therapy Oncology Group 0617 Randomized Clinical Trial.

PubMed

Movsas, Benjamin; Hu, Chen; Sloan, Jeffrey; Bradley, Jeffrey; Komaki, Ritsuko; Masters, Gregory; Kavadi, Vivek; Narayan, Samir; Michalski, Jeff; Johnson, Douglas W; Koprowski, Christopher; Curran, Walter J; Garces, Yolanda I; Gaur, Rakesh; Wynn, Raymond B; Schallenkamp, John; Gelblum, Daphna Y; MacRae, Robert M; Paulus, Rebecca; Choy, Hak

2016-03-01

A recent randomized radiation dose-escalation trial in unresectable stage III non-small-cell lung cancer (NSCLC) (Radiation Therapy Oncology Group [RTOG] 0617) showed a lower survival rate in the high-dose radiation therapy (RT) arm (74 Gy) than in the low-dose arm (60 Gy) with concurrent chemotherapy. The primary QOL hypothesis predicted a clinically meaningful decline in quality of life (QOL) via the Functional Assessment of Cancer Therapy (FACT)-Lung Cancer Subscale (LCS) in the high-dose RT arm at 3 months. The RTOG 0617 trial was a randomized phase 3 study (conducted from November 2007 to November 2011) in stage III NSCLC using a 2 × 2 factorial design and stratified by histology, positron emission tomography staging, performance status, and irradiation technique (3-dimensional conformal RT [3D-CRT] vs intensity-modulated RT [IMRT]). A total of 185 institutions in the United States and Canada took part. Of 424 eligible patients with stage III NSCLC randomized, 360 (85%) consented to QOL evaluation, of whom 313 (88%) completed baseline QOL assessments. Treatment with 74-Gy vs 60-Gy RT with concurrent and consolidation carboplatin/paclitaxel with or without cetuximab. The QOL data were collected prospectively via FACT Trial Outcome Index (FACT-TOI), calculated as the sum of the following measures: Physical Well Being (PWB), Functional Well Being (FWB), and the LCS. Data are presented at baseline and 3 and 12 months via minimal clinically meaningful changes of 2 points or more for PWB, FWB, and LCS or 5 points or more for TOI. Of the 313 patients who completed baseline QOL assessments, 219 patients (70%) completed the 3-month QOL assessments, and 137 of the living patients (57%) completed the 12-month assessment. Patient demographics and baseline QOL scores were comparable between the 74-Gy and 60-Gy arms. Significantly more patients in the 74-Gy arm than in the 60-Gy arm had clinically meaningful decline in FACT-LCS at 3 months (45% vs 30%; P = .02). At 12 months, fewer patients who received IMRT (vs 3D-CRT) had clinically meaningful decline in FACT-LCS (21% vs 46%; P = .003). Baseline FACT-TOI was associated with overall survival in multivariate analysis. Despite few differences in clinician-reported toxic effects between treatment arms, QOL analysis demonstrated a clinically meaningful decline in QOL in the 74-Gy arm at 3 months, confirming the primary QOL hypothesis. Baseline QOL was an independent prognostic factor for survival. clinicaltrials.gov Identifier: NCT00533949.

Dentoskeletal Effects of the Modified Tandem Appliance vs the Facemask Appliance in the Treatment of Skeletal Class III Malocclusion: A Single-center, Randomized Controlled Trial.

PubMed

Husson, Amro H; Burhan, Ahmad S; Salma, Fadwa B; Nawaya, Fehmieh R

2016-07-01

The aim of this randomized controlled trial was to compare the skeletal and dentoalveolar effects of the modified tandem appliance (MTA) vs the facemask (FM) with rapid maxillary expansion. Thirty-two patients, aged 7 to 9 years were recruited. Eligibility criteria included skeletal class III malocclusion that resulted from the retrusion of the maxilla. Randomization was accomplished to divide the sample into two equal groups to be treated with either MTA or FM. Lateral cephalometric radiographs were obtained before treatment and after 2 mm positive overjet was achieved. Intragroup comparisons were performed using paired-sample t-test, and intergroup comparisons were performed using two-sample t-test at the p ≤ 0.05 level. Thirty-two patients (16 in each group) were available for statistical analysis. The pretreatment variables of both groups were similar. Both treatment therapies showed similar significant increase in the SNA and ANB angles, accompanied by slight decrease in the SNB angle. The increase in the SN:GoMe angle, Bjork's sum, and the overjet were significantly greater in the FM group. The forward movement of upper dentition was similar in both groups. Although the lower incisors retrusion was significantly greater in the FM group than in the MTA group, the uprighting of the lower molars was significantly greater in the MTA group. Both appliances showed similar effects apart from less clockwise rotation of the mandible, less retrusion of the lower incisors, and greater uprighting of the lower molars in the MTA group. Both the MTA and the FM groups are effective in treating class III malocclusion. The MTA group is more efficient in controlling the clockwise rotation and gaining some space in the lower arch.

POTENTIAL EFFECTS OF WHOLE-BODY VIBRATION EXERCISES ON BLOOD FLOW KINETICS OF DIFFERENT POPULATIONS: A SYSTEMATIC REVIEW WITH A SUITABLE APPROACH.

PubMed

Sá-Caputo, Danúbia; Paineiras-Domingos, Laisa; Carvalho-Lima, Rafaelle; Dias-Costa, Glenda; de Paiva, Patrícia de Castro; de Azeredo, Claudia Figueiredo; Carmo, Roberto Carlos Resende; Dionello, Carla F; Moreira-Marconi, Eloá; Frederico, Éric Heleno F F; Sousa-Gonçalves, Cintia Renata; Morel, Danielle S; Paiva, Dulciane N; Avelar, Núbia C P; Lacerda, Ana C; Magalhães, Carlos E V; Castro, Leonardo S; Presta, Giuseppe A; de Paoli, Severo; Sañudo, Borja; Bernardo-Filho, Mario

2017-01-01

The ability to control skin blood flow decreases with advancing age and some clinical disorders, as in diabetes and in rheumatologic diseases. Feasible clinical strategies such as whole-body vibration exercise (WBVE) are being used without a clear understanding of its effects. The aim of the present study is to review the effects of the WBVE on blood flow kinetics and its feasibility in different populations. The level of evidence (LE) of selected papers in PubMed and/or PEDRo databases was determined. We selected randomized, controlled trials in English to be evaluated. Six studies had LE II, one had LE III-2 and one III-3 according to the NHMRC. A great variability among the protocols was observed but also in the assessment devices; therefore, more research about this topic is warranted. Despite the limitations, it is can be concluded that the use of WBVE has proven to be a safe and useful strategy to improve blood flow. However, more studies with greater methodological quality are needed to clearly define the more suitable protocols.

Frequency of second mesiobuccal canal in permanent maxillary first molars using the operating microscope and selective dentin removal: A clinical study.

PubMed

Das, Suroopa; Warhadpande, Manjusha M; Redij, Saurabh A; Jibhkate, N G; Sabir, Husain

2015-01-01

The aim of this study was to investigate whether the combination of operating microscope and selective dentin removal increased the frequency of second mesiobuccal (MB2) canal detection in permanent maxillary first molar teeth. One hundred fifty permanent maxillary first molars indicated for root canal treatment were randomly selected from patients belonging to the age group of 18-45 years irrespective of gender. After access cavity preparation and location of main canals, the MB2 canal orifice was sought in all teeth with an endodontic explorer under direct vision (Stage I), then under magnification with the aid of operating microscope (Stage II) and finally with the combined use of operating microscope and selective dentin removal (Stage III). MB2 canals were detected in 36%, 54% and 72% of the teeth in Stages I-III, respectively. This study demonstrated that dental operating microscope when used along with adjunctive aids such as selective dentin removal/troughing and good clinical knowledge will increase the ability of dental clinician to locate MB2 canals.

The FIND-CKD study--a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale.

PubMed

Macdougall, Iain C; Bock, Andreas; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Cushway, Timothy; Roger, Simon D

2014-04-01

Rigorous data are sparse concerning the optimal route of administration and dosing strategy for iron therapy with or without concomitant erythropoiesis-stimulating agent (ESA) therapy for the management of iron deficiency anaemia in patients with non-dialysis dependent chronic kidney disease (ND-CKD). FIND-CKD was a 56-week, open-label, multicentre, prospective, randomized three-arm study (NCT00994318) of 626 patients with ND-CKD and iron deficiency anaemia randomized to (i) intravenous (IV) ferric carboxymaltose (FCM) at an initial dose of 1000 mg iron with subsequent dosing as necessary to target a serum ferritin level of 400-600 µg/L (ii) IV FCM at an initial dose of 200 mg with subsequent dosing as necessary to target serum ferritin 100-200 µg/L or (iii) oral ferrous sulphate 200 mg iron/day. The primary end point was time to initiation of other anaemia management (ESA therapy, iron therapy other than study drug or blood transfusion) or a haemoglobin (Hb) trigger (two consecutive Hb values <10 g/dL without an increase of ≥ 0.5 g/dL). The background, rationale and study design of the trial are presented here. The study has been completed and results are expected in late 2013. FIND-CKD was the longest randomized trial of IV iron therapy to date. Its findings will address several unanswered questions regarding iron therapy to treat iron deficiency anaemia in patients with ND-CKD. It was also the first randomized trial to utilize both a high and low serum ferritin target range to adjust IV iron dosing, and the first not to employ Hb response as its primary end point.

Electro-acupuncture for pain relief after nasal septoplasty: a randomized controlled study.

PubMed

Sahmeddini, Mohammad A; Farbood, Arash; Ghafaripuor, Sina

2010-01-01

Electro-acupuncture (EA) can be effective in some pain conditions, but still there have been no randomized controlled studies of EA for treatment of acute postoperative pain in nasal septoplasty. Therefore, we did a study to test whether EA of specific points is superior to sham acupuncture for complementary analgesia after nasal septoplasty. Ninety (90) patients with an American Society of Anesthesiology (ASA) physical status of I-II scheduled for elective septoplasty were randomly allocated to acupuncture group or control group. Postoperative pain was treated with intravenous meperidine. The time to the first analgesic request, and pain intensity on a 100-mm visual analogue scale (VAS-100) were used to evaluate postoperative pain, and the amount of postoperative meperidine and incidence of analgesia related to side-effects were recorded. Postoperative pain intensity on VAS-100 and respiratory depression were similar in both groups (p > 0.05), but nausea and vomiting were less in the acupuncture group than in the control group (p < 0.05). Findings from our study demonstrate that both uses of EA and 0.1 mg/kg IV morphine given intraoperatively resulted in a similar postoperative pain score, and meperidine was not given in any patient in the two groups during postoperative period because the VAS scores of all patients were less than 40 mm.

Risperidone Added to Psychostimulant in Children with Severe Aggression and Attention-Deficit/Hyperactivity Disorder: Lack of Effect on Attention and Short-Term Memory.

PubMed

Farmer, Cristan A; Epstein, Jeffery N; Findling, Robert L; Gadow, Kenneth D; Arnold, L Eugene; Kipp, Heidi; Kolko, David J; Butter, Eric; Schneider, Jayne; Bukstein, Oscar G; McNamara, Nora K; Molina, Brooke S G; Aman, Michael G

2017-03-01

Professionals have periodically expressed concern that atypical antipsychotics may cause cognitive blunting in treated patients. In this study, we report data from a double-blind, randomized, controlled study of stimulant plus placebo versus combined stimulant and risperidone to evaluate the effects of the atypical antipsychotic on attention and short-term memory. A total of 165 (n = 83 combined treatment; n = 82 stimulant plus placebo) children with attention-deficit/hyperactivity disorder and severe physical aggression, aged 6-12 years, were evaluated with Conners' Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children-III (WISC) Digit Span subscale at baseline, after 3 weeks of stimulant-only treatment, and after six additional weeks of randomized treatment (stimulant+placebo vs. stimulant+risperidone). At 3 weeks, improvement on CPT-II performance (Commissions and Reaction Time Standard Error; p < 0.001) and on Digit Span memory performance (p < 0.006) was noted for the full sample. At study week 9, no difference in CPT-II or Digit Span performance was observed between the randomized groups (ps = 0.41 to 0.83). Similar to other studies, we found no deleterious effects on attention and short-term memory associated with short-term use of risperidone. NCT00796302.

Study of Pharmacodynamic and Pharmacokinetic Interaction of Bojungikki-Tang with Aspirin in Healthy Subjects and Ischemic Stroke Patients

PubMed Central

Yoo, Jung-Hwa; Yim, Sung-Vin

2018-01-01

Background Bojungikki-tang (BJIKT) is a widely used traditional herbal formula in China, Japan, and Korea. There have been reports that several herbs among BJIKT have interactions with antiplatelet drugs, such as aspirin. This study aimed to assess whether BJIKT interacts with aspirin in terms of pharmacokinetics (PK) and pharmacodynamics (PD) in healthy subjects and ischemic stroke patients. Methods The phase I interaction trial was a randomized, open-label, crossover study of 10 healthy male subjects, and the phase III interaction trial was a randomized, placebo-controlled, parallel study of 43 ischemic stroke patients. Each participant randomly received aspirin + BJIKT or aspirin + placebo. For PK analysis, plasma acetyl salicylic acid (ASA) and salicylic acid (SA) were evaluated, and, for PD analysis, platelet aggregation and plasma thromboxane B2 (TxB2) were measured. Results In the PK parameters, mean area under curve, maximum concertation, and peak concentration time of ASA and SA were not different between two groups in healthy subjects and ischemic stroke patients. In the PD profiles, TxB2 concentrations and platelet aggregation were not affected by coadministration of BJIKT in healthy subjects and ischemic stroke patients. Conclusions These results suggest that coadministration of BJIKT with aspirin may not result in herb-drug interaction. PMID:29599812

The reliability of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF) definitions in diagnosing metabolic syndrome (MetS) among Gaza Strip Palestinians.

PubMed

Sirdah, Mahmoud M; Abu Ghali, Asmaa S; Al Laham, Nahed A

2012-01-01

Metabolic syndrome (MetS) which is a multifaceted syndrome, has been demonstrated as a common precursor for developing cardiovascular diseases and/or type 2 diabetes mellitus. Different diagnostic definitions for MetS have been proposed and recommended. We set up to evaluate the reliabilities of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF) definitions in diagnosing MetS among Gaza Strip Palestinians. This cross sectional study involved a randomly selected two hundred and thirty apparently healthy adults from the Gaza Strip. Anthropometric measurements, blood pressure, fasting plasma glucose, lipid profile, and questionnaire interviews were performed. The overall prevalence of MetS in our Gaza Strip cohort was 23.0% and 39.5% according to NCEP/ATP III and IDF definitions respectively (p<0.001). No significant differences were seen in the number of MetS components in individuals having MetS by either definition (mean 3.42 ± 0.63 vs 3.52 ± 0.69 respectively, p=0.865). Both IDF and NCEP/ATP III showed an increased prevalence of MetS with age, and body mass index (BMI), however they revealed different prevalence trends with sex. Except for BMI, there were no significant differences in the general and metabolic related characteristics between subjects with MetS of IDF and NCEP/ATP III definitions. Independently of the definition used, MetS is highly prevalent in Gaza Strip population, with a steady increase in MetS prevalence through age and BMI. The IDF definition tends to give higher values for MetS prevalence, and therefore could be more appropriate for diagnosing MetS in Gaza Strip cohort. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Efficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleeding.

PubMed

Abd ElRahim, Ayman Yosry; Fouad, Rabab; Khairy, Marwa; Elsharkawy, Aisha; Fathalah, Waleed; Khatamish, Haytham; Khorshid, Omayma; Moussa, Mona; Seyam, Moataz

2018-01-01

Band ligation and propranolol are the current therapies for primary prevention of variceal bleeding. Carvedilol is a rising nonselective beta-blocker used for reducing portal pressure with favorable outcome. The aim of this study to assess the efficacy of carvedilol, propranolol, and band ligation for primary prevention of variceal bleeding based on the effect of each regimen on progression of Child score and portal hypertensive gastropathy after 1 year. The study included 264 cirrhotic patients with medium/large-sized varices who were candidates for primary prophylaxis of variceal bleeding. Patients were randomly divided into three groups: group I: band ligation; group II: propranolol; group III: carvedilol. Group I showed higher success rate of 75 %, followed by group III with 70.2 % and group II with 65.2 %. Risk of bleeding was comparable between the three groups, with group II carrying the highest rate of complications (34.7 %) followed by group III (14.2 %) and finally group I (5.7 %). After 1 year of follow-up, Child score did not improve in any of the studied groups, while portal hypertensive gastropathy significantly increased in group I but decreased in groups II and III. Band ligation is the best treatment option for primary prevention of variceal bleeding with minimal complications. Carvedilol is a good pharmaceutical alternative medicine to propranolol with lesser side-effects. Progress of liver disease as represented by Child score is not affected by any of the primary variceal prophylactic regimens, although medical treatment reduces portal hypertensive gastropathy. Choice of treatment depends on patient will, compliance with treatment, and endoscopist competence.

Biological Therapies: Effects of Proinflammatory Pathways and their Inhibition on the Myocardium of Rheumatoid Athritis Patients.

PubMed

Obermair, Florian; Pieringer, Herwig

2015-01-01

The elevated risk of heart failure (HF) in rheumatoid arthritis (RA) is considered to be partly caused by the chronic low-grade systemic inflammation. As potent suppressors of inflammation, biologics were expected to influence HF development in RA. Unfortunately, case reports of HF in RA patients and non-RA HF studies have suggested that these drugs may even increase HF rates in RA. With this review we want to provide insight into the molecular mechanisms by which elevated cytokines, immune cell alterations and biologics influence myocardial function in RA patients. Beside preclinical data, clinical studies that assess the influence of biologics on HF development are reviewed. Preclinical studies suggest a bidirectional role of the investigated cytokines (TNF-alpha, IL- 1, IL-6) on myocardial function. Common mechanisms of immune cell alterations in HF and RA have been observed in preclinical studies. High doses of infliximab in non-RA patients with HF were found to be harmful. The vast majority of retrospective studies suggest that TNF-alpha inhibitors do not increase the risk of HF development in RA patients. Nevertheless randomized controlled trials are missing and TNF-alpha inhibitors are contraindicated in RA patients with HF NYHA III/IV and should be used with caution in RA patients with HF NYHA I/II based on non-RA HF studies. Due to rare adverse events of HF, rituximab is contraindicated in RA patients with HF NYHA IV. Cytokines seem to have a bidirectional influence on HF development in RA. According to the published evidence it is unlikely that TNFalpha inhibitors substantially increase the risk of HF development in an RA population. Nevertheless they are contraindicated in RA patients with HF NYHA III/IV and should be used with caution in RA patients with HF NYHA I/II. The influence of anakinra, tocilizumab, rituximab and abatacept needs to be investigated in future studies.

Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study.

PubMed

Fernández, Oscar; Izquierdo, Guillermo; Fernández, Victoria; Leyva, Laura; Reyes, Virginia; Guerrero, Miguel; León, Antonio; Arnaiz, Carlos; Navarro, Guillermo; Páramo, Maria Dolores; Cuesta, Antonio De la; Soria, Bernat; Hmadcha, Abdelkrim; Pozo, David; Fernandez-Montesinos, Rafael; Leal, Maria; Ochotorena, Itziar; Gálvez, Patricia; Geniz, Maria Angeles; Barón, Francisco Javier; Mata, Rosario; Medina, Cristina; Caparrós-Escudero, Carlos; Cardesa, Ana; Cuende, Natividad

2018-01-01

Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded. Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy. Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique.

Brush Day & Night Phase III to Phase IV: ensuring that good oral health habits are sustainable.

PubMed

Melo, Paulo; Fine, Charlotte; Malone, Sinead; Horn, Virginie

2018-05-01

Over the past 10 years, the FDI-Unilever Brush Day & Night partnership has significantly influenced the life of children worldwide through the implementation of school programmes for oral health education and prevention. This article reports the key facts and outcomes of Phase III of the partnership, and announces the launch of Phase IV. During Phase III, the expert advisors of the Brush Day & Night partnership conducted a longitudinal study to evaluate the impact of the '21 Day' programme in almost 8,000 children in 10 countries. Analysis revealed the effectiveness of the 21 Day programme in sustainably educating children to brush their teeth twice a day, with the greatest impact observed in children aged 7-9 years. With the launch of Phase IV, the Brush Day & Night partnership will continue to deliver its oral health school programme for 7-9 year-old children with a strengthened methodology, including randomized sampling and control groups. The scope of the evaluation will be broadened to include oral health-related quality of life indicators, and monitoring of the oral health knowledge of children's parents/carers. © 2018 FDI World Dental Federation.

Effects of joint position on the distraction distance during grade III glenohumeral joint distraction in healthy individuals

PubMed Central

Park, Sam-Sik; Kim, Bo-Kyung; Moon, Ok-Kon; Choi, Wan-Suk

2015-01-01

[Purpose] The study investigated the effects of joint position on the distraction distance during Grade III glenohumeral joint distraction in healthy individuals. [Subjects and Methods] Twenty adults in their forties without shoulder disease were randomly divided into neutral position group (NPG; n = 7), resting position group (RPG; n = 7), and end range position group (ERPG; n = 6). After Kaltenborn Grade III distraction for 40s, the distance between glenoid fossa and humeral head was measured by ultrasound. [Results] The average distances between the humeral head and glenoid fossa before distraction were 2.86 ± 0.81, 3.21 ± 0.47, and 3.55 ± 0.59 mm for the NP, RP, and ERP groups. The distances after applying distraction were 3.12 ± 0.51, 3.86 ± 0.55, and 4.35 ± 0.32 mm. Between-group comparison after applying distraction revealed no significant differences between the NP and RP groups, while there was a statistically significant difference between the NP and RP groups, as well as between the NP and ERP groups. [Conclusion] Joint space was largest in ERP individuals when performing manual distraction. PMID:26644692

Pathologic changes of wound tissue in rats with stage III pressure ulcers treated by transplantation of human amniotic epithelial cells.

PubMed

Zheng, Xilan; Jiang, Zhixia; Zhou, Aiting; Yu, Limei; Quan, Mingtao; Cheng, Huagang

2015-01-01

This study aims to determine the impact of orthotopic transplantation of human amniotic epithelial cells (hAECs) on the pathologic changes of wound tissues in a self-prepared rat stage III pressure ulcer model. Ninety-six SD rats were randomly divided into the model group (group M), hAEC transplantation group (group H), traditional treatment group (group T), and the control group (group C), with 24 rats in each group. The wound healing time was observed in 6 rats from each group, and 6 rats of each group were selected for post-modeling on day(s) (D) 1, 3, and 7 for HE staining to compare the pathological changes. The healing time of group H was significantly shorter than the other three groups. Moreover, pathological observations revealed that group H exhibited significant proliferation of fibrous tissues and vessels in the dermal layer, and the appearance time and degree of skin appendages were significantly greater than that observed in the other three groups. Pathological observations showed that hAEC transplantation could significantly speed up the healing of stage III pressure ulcer.

Cancer chemoprevention research with selenium in the post-SELECT era: Promises and challenges

PubMed Central

Lü, Junxuan; Zhang, Jinhui; Jiang, Cheng; Deng, Yibin; Özten, Nur; Bosland, Maarten C.

2016-01-01

The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of non-small cell lung cancer (NSCLC) in North America lead to rejection of SeMet/Se-yeast for cancer prevention in Se-adequate populations. We identify two major lessons from the outcomes of these trials: 1) The antioxidant hypothesis was tested in wrong subjects or patient populations. 2) The selection of Se agents was not supported by cell culture and preclinical animal efficacy data as is common in drug development. We propose that next-generation forms of Se (next-gen Se), such as methylselenol precursors, offer biologically appropriate approaches for cancer chemoprevention but these are faced with formidable challenges. Solid mechanism-based preclinical efficacy assessments and comprehensive safety studies with next-gen Se will be essential to re-vitalize the idea of cancer chemoprevention with Se in the post-SELECT era. We advocate smaller mechanism-driven Phase I/II trials with these next-gen Se to guide and justify future decisions for definitive Phase III chemoprevention efficacy trials. PMID:26595411

Cancer chemoprevention research with selenium in the post-SELECT era: Promises and challenges.

PubMed

Lü, Junxuan; Zhang, Jinhui; Jiang, Cheng; Deng, Yibin; Özten, Nur; Bosland, Maarten C

2016-01-01

The negative efficacy outcomes of double-blinded, randomized, placebo-controlled Phase III human clinical trials with selenomethionine (SeMet) and SeMet-rich selenized-yeast (Se-yeast) for prostate cancer prevention and Se-yeast for prevention of nonsmall cell lung cancer (NSCLC) in North America lead to rejection of SeMet/Se-yeast for cancer prevention in Se-adequate populations. We identify 2 major lessons from the outcomes of these trials: 1) the antioxidant hypothesis was tested in wrong subjects or patient populations, and 2) the selection of Se agents was not supported by cell culture and preclinical animal efficacy data as is common in drug development. We propose that next-generation forms of Se (next-gen Se), such as methylselenol precursors, offer biologically appropriate approaches for cancer chemoprevention but these are faced with formidable challenges. Solid mechanism-based preclinical efficacy assessments and comprehensive safety studies with next-gen Se will be essential to revitalize the idea of cancer chemoprevention with Se in the post-SELECT era. We advocate smaller mechanism-driven Phase I/II trials with these next-gen Se to guide and justify future decisions for definitive Phase III chemoprevention efficacy trials.

A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III.

PubMed

Morgia, Giuseppe; Russo, Giorgio Ivan; Urzì, Daniele; Privitera, Salvatore; Castelli, Tommaso; Favilla, Vincenzo; Cimino, Sebastiano

2017-06-30

The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A) or treatment (Group B). Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95%) and Calendula extract 80 mg (1 suppository/die for 1 month). Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT). A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01), IIEF-5 (+ 3.5; p < 0.01), PEDT (-6.5; p < 0.01), peak flow (+2.8; p < 0.01) and VAS (-6.5; p < 0.01) with significant differences over placebo group (all p-value significant). In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of inflammatory cells. These results should be confirmed in further studies with greater sample size.

Effect of transcutaneous electrical stimulation treatment on lower urinary tract symptoms after class III radical hysterectomy in cervical cancer patients: study protocol for a multicentre, randomized controlled trial.

PubMed

Sun, Xiu-Li; Wang, Hai-Bo; Wang, Zhi-Qi; Cao, Ting-Ting; Yang, Xin; Han, Jing-Song; Wu, Yang-Feng; Reilly, Kathleen H; Wang, Jian-Liu

2017-06-15

Class III radical hysterectomy (RH III)_plus pelvic lymphadenectomy is the standard surgery for early stage cervical cancer (CC) patients, the 5 year survival rate is about 90%, but pelvic floor disorders especially bladder dysfunction are common due to damaged vessels and nerve fibers following surgery. Transcutaneous electrical stimulation (TENS) treatment has been used to treat bladder disorders for many years, but its effect on cervical cancer patients, the best treatment time point and stimulated protocol, had never been assessed. The aim of this study is to investigate the efficacy of TENS treatment on lower urinary tract symptoms (LUTS) after RH III in CC patients. The study will be conducted as a clinical, multicentre, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 208 participants (at 1:1 ratio, 104 subjects in each group). At 5-7 days after RH III, patients are screened according to operative and pathological findings. Enrolled participants are randomised into an intervention group (TENS plus conventional clinical care) or control group (conventional clinical care), with stratification by menopausal status (menopause vs. non-menopause) and surgical modality (laparoscopic RH or abdominal RH). Participants in both groups will be followed up at 14 days, 21 days, 28 days, 3 months, 6 months, 12 months, 18 months and 24 months after surgery. The primary endpoint is improvement rate of urination function which is defined as recovery (residual urine ≤50 ml) or improvement (residual urine 50-100 ml). Secondary endpoints include urodynamic parameter, urinary incontinence, anorectal function, pelvic function, quality of life (QOL), disease-free survival and adverse events. Primary endpoint analyses will be carried out by Cochran-Mantel-Haenszel tests taking into center effect. To our knowledge this is the first trial to investigate the effect of TENS treatment on bladder function recovery after RH III among CC patients. This study will provide new information on TENS efficacy for bladder function recovery. Once confirmed, it may help to provide a new, non-invisive treatment for those postoperative CC patients with poor pelvic function, which would help improve their quality of life. The study is registered to Clinical Trials.gov ( NCT02492542 ) on June 25, 2015.

A methods review on use of nonsense suppression to study 3′ end formation and other aspects of tRNA biogenesis

PubMed Central

Rijal, Keshab; Maraia, Richard J.; Arimbasseri, Aneeshkumar G.

2014-01-01

Suppressor tRNAs bear anticodon mutations that allow them to decode premature stop codons in metabolic marker gene mRNAs, that can be used as in vivo reporters of functional tRNA biogenesis. Here, we review key components of a suppressor tRNA system specific to S. pombe and its adaptations for use to study specific steps in tRNA biogenesis. Eukaryotic tRNA biogenesis begins with transcription initiation by RNA polymerase (pol) III. The nascent pre-tRNAs must undergo folding, 5′ and 3′ processing to remove the leader and trailer, nuclear export, and splicing if applicable, while multiple complex chemical modifications occur throughout the process. We review evidence that precursor-tRNA processing begins with transcription termination at the oligo(T) terminator element, which forms a 3′ oligo(U) tract on the nascent RNA, a sequence-specific binding site for the RNA chaperone, La protein. The processing pathway bifurcates depending on a poorly understood property of pol III termination that determines the 3′ oligo(U) length and therefore the affinity for La. We thus review the pol III termination process and the factors involved including advances using gene-specific random mutagenesis by dNTP analogs that identify key residues important for transcription termination in certain pol III subunits. The review ends with a ‘technical approaches’ section that includes a parts lists of suppressor-tRNA alleles, strains and plasmids, and graphic examples of its diverse uses. PMID:25447915

Can contrast-enhanced ultrasonography improve Zone III REBOA placement for prehospital care?

PubMed

Chaudery, Muzzafer; Clark, James; Morrison, Jonathan J; Wilson, Mark H; Bew, Duncan; Darzi, Ara

2016-01-01

Torso hemorrhage is the primary cause of potentially preventable mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been advocated as an adjunct to bridge patients to definitive hemorrhage control. The primary aim of this study was to assess whether contrast-enhanced ultrasonography can improve the accuracy of REBOA placement in the infrarenal aorta (Zone III). A fluoroscopy-free "enhanced" Zone III REBOA technique was developed using a porcine cadaver model. A "standard" over-the-wire Seldinger technique was used, which was enhanced with the addition of a microbubble contrast medium to inflate the balloon, observed with ultrasonography. Following this, attending- and resident-level physicians were randomized into two groups. They were taught either the enhanced with ultrasonography guidance (Group A) or the standard measuring length of catheter insertion (Group B) technique as part of a human cadaver trauma skills course. Outcomes assessed included time (seconds) from insertion to inflation, accuracy, and missed targets. All results were benchmarked against three endovascular experts. There were 20 participants who performed REBOA with Group A (51 [31]) being significantly faster than Group B (90 [63]) (p = 0.003) and more accurate (p = 0.023) with no missed targets. Group B had five missed targets, the most common error being inflation within Zone II. For Zone III REBOA, contrast-enhanced ultrasonography technique is faster and more accurate than the standard technique. This may have value in time-critical and austere environments. Clinical studies are now required to evaluate this approach further.

Pain Elimination during Injection with Newer Electronic Devices: A Comparative Evaluation in Children.

PubMed

Bansal, Neha; Saha, Sonali; Jaiswal, Jn; Samadi, Firoza

2014-05-01

The present study was taken up to clinically evaluate and compare effectiveness of transcutaneous electrical nerve stimulator (TENS) and comfort control syringe (CCS) in various pediatric dental procedures as an alternative to the conventional method of local anesthesia (LA) administration. Ninety healthy children having at least one deciduous molar tooth indicated for extraction in either maxillary right or left quadrant in age group of 6 to 10 years were randomly divided into three equal groups having 30 subjects each. Group I: LA administration using conventional syringe, group II: LA administration using TENS along with the conventional syringe, group III: LA administration using CCS. After LA by the three techniques, pain, anxiety and heart rate were measured. The observations, thus, obtained were subjected to statistical analysis using analysis of variance (ANOVA), student t-test and paired t-test. The mean pain score was maximum in group I followed by group II, while group III revealed the minimum pain, where LA was administered using CCS. Mean anxiety score was maximum in group I followed by group II, while group III revealed the minimum score. Mean heart rate was maximum in group I followed in descending order by groups II and III. The study supports the belief that CCS could be a viable alternative in comparison to the other two methods of LA delivery in children. How to cite this article: Bansal N, Saha S, Jaiswal JN, Samadi F. Pain Elimination during Injection with Newer Electronic Devices: A Comparative Evaluation in Children. Int J Clin Pediatr Dent 2014;7(2):71-76.

A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group.

PubMed

Pautier, P; Floquet, A; Gladieff, L; Bompas, E; Ray-Coquard, I; Piperno-Neumann, S; Selle, F; Guillemet, C; Weber, B; Largillier, R; Bertucci, F; Opinel, P; Duffaud, F; Reynaud-Bougnoux, A; Delcambre, C; Isambert, N; Kerbrat, P; Netter-Pinon, G; Pinto, N; Duvillard, P; Haie-Meder, C; Lhommé, C; Rey, A

2013-04-01

There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). API adjuvant CT statistically increases the 3 year-DFS of patients with US.

Impact of Availability of Companion Diagnostics on the Clinical Development of Anticancer Drugs.

PubMed

Tibau, Ariadna; Díez-González, Laura; Navarro, Beatriz; Galán-Moya, Eva M; Templeton, Arnoud J; Seruga, Bostjan; Pandiella, Atanasio; Amir, Eitan; Ocana, Alberto

2017-06-01

Companion diagnostics permit the selection of patients likely to respond to targeted anticancer drugs; however, it is unclear if the drug development process differs between drugs developed with or without companion diagnostics. Identification of differences in study design could help future clinical development. Anticancer drugs approved for use in solid tumors between 28 September 2000 and 4 January 2014 were identified using a search of the US FDA website. Phase III trials supporting registration were extracted from the drug label. Each published study was reviewed to obtain information about the phase I and II trials used for the development of the respective drug. We identified 35 drugs and 59 phase III randomized trials supporting regulatory approval. Fifty-three phase I trials and 47 phase II trials were cited in the studies and were used to support the design of these phase III trials. The approval of drugs using a companion diagnostic has increased over time (p for trend 0.01). Expansion cohorts were more frequently observed with drugs developed with a companion diagnostic (62 vs. 20%; p = 0.005). No differences between drugs developed with or without a companion diagnostic were observed for the design of phase I and II studies. The approval of drugs developed with a companion diagnostic has increased over time. The availability of a companion diagnostic was associated with more frequent use of phase I expansion cohorts comprising patients selected by the companion diagnostic.

Embedded random matrix ensembles from nuclear structure and their recent applications

NASA Astrophysics Data System (ADS)

Kota, V. K. B.; Chavda, N. D.

Embedded random matrix ensembles generated by random interactions (of low body rank and usually two-body) in the presence of a one-body mean field, introduced in nuclear structure physics, are now established to be indispensable in describing statistical properties of a large number of isolated finite quantum many-particle systems. Lie algebra symmetries of the interactions, as identified from nuclear shell model and the interacting boson model, led to the introduction of a variety of embedded ensembles (EEs). These ensembles with a mean field and chaos generating two-body interaction generate in three different stages, delocalization of wave functions in the Fock space of the mean-field basis states. The last stage corresponds to what one may call thermalization and complex nuclei, as seen from many shell model calculations, lie in this region. Besides briefly describing them, their recent applications to nuclear structure are presented and they are (i) nuclear level densities with interactions; (ii) orbit occupancies; (iii) neutrinoless double beta decay nuclear transition matrix elements as transition strengths. In addition, their applications are also presented briefly that go beyond nuclear structure and they are (i) fidelity, decoherence, entanglement and thermalization in isolated finite quantum systems with interactions; (ii) quantum transport in disordered networks connected by many-body interactions with centrosymmetry; (iii) semicircle to Gaussian transition in eigenvalue densities with k-body random interactions and its relation to the Sachdev-Ye-Kitaev (SYK) model for majorana fermions.

Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients.

PubMed

Gross, Oliver; Friede, Tim; Hilgers, Reinhard; Görlitz, Anke; Gavénis, Karsten; Ahmed, Raees; Dürr, Ulrike

2012-01-01

Introduction. Retrospective observational data show that ACE-inhibitor therapy delays renal failure and improves life expectancy in Alport patients with proteinuria. The EARLY PRO-TECT Alport trial assesses the safety and efficacy of early therapy onset with ramipril in pediatric Alport patients. Methods and analysis. This double-blind, randomized, placebo-controlled, multicenter phase III trial (NCT01485978; EudraCT-number 2010-024300-10) includes 120 pediatric patients aged 24 months to 18 years with early stages of Alport syndrome (isolated hematuria or microalbuminuria). From March 2012, up to 80 patients will be randomized 1:1 to ramipril or placebo. In the event of disease progression during 3-year treatment, patients are unblinded and ramipril is initiated, if applicable. Approximately 40 patients receive open-label ramipril contributing to the safety database. Primary end-points are "time to progression to next disease level" and "incidence of adverse drug events before disease progression." Treatment effect estimates from the randomized comparison and Alport registry data will be combined in supportive analyses to maximize evidence. Conclusion. Without this trial, ACE inhibitors may become standard off-label treatment in Alport syndrome without satisfactory evidence base. The results are expected to be of relevance for therapy of all pediatric patients with kidney disease, and the trial protocol might serve as a model for other rare pediatric glomerulopathies.

Patient-reported outcomes in a phase iii study of everolimus versus placebo in patients with metastatic carcinoma of the kidney that has progressed on vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy.

PubMed

Beaumont, Jennifer L; Butt, Zeeshan; Baladi, Jeanfrancois; Motzer, Robert J; Haas, Tomas; Hollaender, Norbert; Kay, Andrea; Cella, David

2011-01-01

A phase III, randomized, double-blind, placebo-controlled trial was conducted in patients with metastatic renal cell carcinoma. The focus of this paper is to evaluate the patient-reported outcomes. Patients were randomly assigned (2:1) to receive oral everolimus 10 mg once daily or placebo. The Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease-Related Symptoms (FKSI-DRS) and European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 were administered before randomization and on day 1 of each cycle. The FKSI-DRS and the EORTC QLQ-C30 Physical Functioning and Global Quality of Life scores were the primary endpoints examined. Longitudinal models were used to compare treatment arms. Sensitivity analyses were conducted to explore the impact of missing data assumptions. Longitudinal trends for FKSI-DRS scores did not differ by treatment arm. Taking nonignorable missing data into account, there were significant differences between treatment arms in the trend over time for physical functioning and global quality of life, with the everolimus arm exhibiting greater decreases. All three of these measures of health-related quality of life were significantly related to progression-free survival. There was no evidence of a difference between everolimus and placebo in longitudinal patterns of disease-related symptoms, and little difference between the arms in physical functioning or global quality of life trends. This supports the conclusion that delay in tumor progression demonstrated by everolimus is associated with minimal impact on symptoms, physical functioning, or quality of life, as reported by patients.

Patient-Reported Outcomes in a Phase III Study of Everolimus Versus Placebo in Patients with Metastatic Carcinoma of the Kidney That Has Progressed on Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy

PubMed Central

Butt, Zeeshan; Baladi, Jeanfrancois; Motzer, Robert J.; Haas, Tomas; Hollaender, Norbert; Kay, Andrea; Cella, David

2011-01-01

Purpose. A phase III, randomized, double-blind, placebo-controlled trial was conducted in patients with metastatic renal cell carcinoma. The focus of this paper is to evaluate the patient-reported outcomes. Methods. Patients were randomly assigned (2:1) to receive oral everolimus 10 mg once daily or placebo. The Functional Assessment of Cancer Therapy Kidney Symptom Index—Disease-Related Symptoms (FKSI-DRS) and European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 were administered before randomization and on day 1 of each cycle. The FKSI-DRS and the EORTC QLQ-C30 Physical Functioning and Global Quality of Life scores were the primary endpoints examined. Longitudinal models were used to compare treatment arms. Sensitivity analyses were conducted to explore the impact of missing data assumptions. Results. Longitudinal trends for FKSI-DRS scores did not differ by treatment arm. Taking nonignorable missing data into account, there were significant differences between treatment arms in the trend over time for physical functioning and global quality of life, with the everolimus arm exhibiting greater decreases. All three of these measures of health-related quality of life were significantly related to progression-free survival. Conclusions. There was no evidence of a difference between everolimus and placebo in longitudinal patterns of disease-related symptoms, and little difference between the arms in physical functioning or global quality of life trends. This supports the conclusion that delay in tumor progression demonstrated by everolimus is associated with minimal impact on symptoms, physical functioning, or quality of life, as reported by patients. PMID:21459902

Tofacitinib improves pruritus and health-related quality of life up to 52 weeks: Results from 2 randomized phase III trials in patients with moderate to severe plaque psoriasis.

PubMed

Feldman, Steven R; Thaçi, Diamant; Gooderham, Melinda; Augustin, Matthias; de la Cruz, Claudia; Mallbris, Lotus; Buonanno, Marjorie; Tatulych, Svitlana; Kaur, Mandeep; Lan, Shuping; Valdez, Hernan; Mamolo, Carla

2016-12-01

Tofacitinib is an oral Janus kinase inhibitor that improves clinical measures of psoriasis. We sought to assess patient-reported outcomes in tofacitinib-treated patients with moderate to severe plaque psoriasis over 52 weeks. In 2 identical, phase III studies (Oral treatment for Psoriasis Trial Pivotal 1 [NCT01276639], n = 901, and Pivotal 2 [NCT01309737], n = 960), patients were randomized 2:2:1 to receive 5 or 10 mg of tofacitinib or placebo, twice daily. At week 16, placebo-treated patients were re-randomized to tofacitinib. Dermatology Life Quality Index score, Itch Severity Item score, Patient Global Assessment score, and patient satisfaction were assessed. Baseline Dermatology Life Quality Index score indicated substantial health-related quality of life impairment. At week 16, a greater proportion of patients achieved Dermatology Life Quality Index score of 1 or less (no effect of psoriasis on health-related quality of life) with tofacitinib 5 and 10 mg twice daily versus placebo (Oral treatment for Psoriasis Trial Pivotal 1/2: 26.7%/28.6% and 40.2%/48.2% vs 4.6%/6.0%, respectively; P < .0001); improvements were maintained through week 52. Similar patterns were observed with Patient Global Assessment. Improvements in itch were particularly rapid, observed 1 day after treatment initiation for both tofacitinib doses versus placebo (P < .05). At week 16, more patients were satisfied with tofacitinib versus placebo (P < .0001). Clinical nonresponders discontinued at week 28. Tofacitinib demonstrated improvement in health-related quality of life and patient-reported symptoms that persisted over 52 weeks. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial.

PubMed

Weiss, Daniel; Walach, Margarete; Meisner, Christoph; Fritz, Melanie; Scholten, Marlieke; Breit, Sorin; Plewnia, Christian; Bender, Benjamin; Gharabaghi, Alireza; Wächter, Tobias; Krüger, Rejko

2013-07-01

Gait and balance disturbances typically emerge in advanced Parkinson's disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson's Disease Rating Scale score (Scale II items 13-15, Scale III items 27-31) at '3-week follow-up'. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the '3-week follow-up'. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no 'global' effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.

Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

PubMed Central

Macciò, Antonio; Madeddu, Clelia; Serpe, Roberto; Massa, Elena; Dessì, Mariele; Panzone, Filomena; Contu, Paolo

2010-01-01

Purpose. A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia—lean body mass (LBM), resting energy expenditure (REE), and fatigue—and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. Patients and Methods. Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. Results. Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. Conclusion. The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents. PMID:20156909

Protocol and recruitment results from a randomized controlled trial comparing group phone-based versus newsletter interventions for weight loss maintenance among rural breast cancer survivors.

PubMed

Befort, Christie A; Klemp, Jennifer R; Fabian, Carol; Perri, Michael G; Sullivan, Debra K; Schmitz, Kathryn H; Diaz, Francisco J; Shireman, Theresa

2014-03-01

Obesity is a risk factor for breast cancer recurrence and death. Women who reside in rural areas have higher obesity prevalence and suffer from breast cancer treatment-related disparities compared to urban women. The objective of this 5-year randomized controlled trial is to compare methods for delivering extended care for weight loss maintenance among rural breast cancer survivors. Group phone-based counseling via conference calls addresses access barriers, is more cost-effective than individual phone counseling, and provides group support which may be ideal for rural breast cancer survivors who are more likely to have unmet support needs. Women (n=210) diagnosed with Stage 0 to III breast cancer in the past 10 years who are ≥ 3 months out from initial cancer treatments, have a BMI 27-45 kg/m(2), and have physician clearance were enrolled from multiple cancer centers. During Phase I (months 0 to 6), all women receive a behavioral weight loss intervention delivered through group phone sessions. Women who successfully lose 5% of weight enter Phase II (months 6 to 18) and are randomized to one of two extended care arms: continued group phone-based treatment or a mail-based newsletter. During Phase III, no contact is made (months 18 to 24). The primary outcome is weight loss maintenance from 6 to 18 months. Secondary outcomes include quality of life, serum biomarkers, and cost-effectiveness. This study will provide essential information on how to reach rural survivors in future efforts to establish weight loss support for breast cancer survivors as a standard of care. Copyright © 2014 Elsevier Inc. All rights reserved.

TRIBE-2: a phase III, randomized, open-label, strategy trial in unresectable metastatic colorectal cancer patients by the GONO group.

PubMed

Cremolini, Chiara; Marmorino, Federica; Loupakis, Fotios; Masi, Gianluca; Antoniotti, Carlotta; Salvatore, Lisa; Schirripa, Marta; Boni, Luca; Zagonel, Vittorina; Lonardi, Sara; Aprile, Giuseppe; Tamburini, Emiliano; Ricci, Vincenzo; Ronzoni, Monica; Pietrantonio, Filippo; Valsuani, Chiara; Tomasello, Gianluca; Passardi, Alessandro; Allegrini, Giacomo; Di Donato, Samantha; Santini, Daniele; Falcone, Alfredo

2017-06-09

Chemotherapy plus bevacizumab is a standard first-line treatment for unresectable metastatic colorectal cancer patients. Different chemotherapy backbones may be chosen, including one to three drugs, based on patients' general conditions and comorbidities, treatments' objectives, and disease characteristics. TRIBE trial demonstrated a significant advantage in terms of progression-free survival and overall survival for FOLFOXIRI plus bevacizumab as compared with FOLFIRI plus bevacizumab. Based on recent evidence, the de-intensification of the upfront regimen after 4-6 months of treatment is nowadays regarded as a valuable option. Moreover, the prolonged inhibition of angiogenesis, and in particular the continuation of bevacizumab beyond the evidence of disease progression, is an efficacious strategy in the treatment of metastatic colorectal cancer patients. TRIBE-2 is a prospective, open-label, multicentric phase III randomized trial in which unresectable and previously untreated metastatic colorectal cancer patients are randomized to receive first-line FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab after disease progression or FOLFOXIRI plus bevacizumab followed by the re-introduction of the same regimen after disease progression. The primary endpoint is to compare the efficacy of the two proposed treatment strategies in terms of Progression Free Survival 2. The TRIBE-2 study aims at answering the question whether the upfront use of FOLFOXIRI improves the clinical outcome of metastatic colorectal cancer patients, when compared with the pre-planned, sequential use of oxaliplatin-based and irinotecan-based doublets. Both proposed treatment strategies are designed to exploit the effectiveness of the prolonged inhibition of angiogenesis, alternating short (up to 4 months) induction periods and less intensive maintenance phases. TRIBE2 is registered at Clinicaltrials.gov: NCT02339116 . January 12, 2015. TRIBE-2 is registered at EUDRACT 2014-004436-19, October 10, 2014.

Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial.

PubMed

Gilbert, Mark R; Wang, Meihua; Aldape, Kenneth D; Stupp, Roger; Hegi, Monika E; Jaeckle, Kurt A; Armstrong, Terri S; Wefel, Jeffrey S; Won, Minhee; Blumenthal, Deborah T; Mahajan, Anita; Schultz, Christopher J; Erridge, Sara; Baumert, Brigitta; Hopkins, Kristen I; Tzuk-Shina, Tzahala; Brown, Paul D; Chakravarti, Arnab; Curran, Walter J; Mehta, Minesh P

2013-11-10

Radiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM. This phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status. A total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P < .001), PFS (8.7 v 5.7 months; HR, 1.63; P < .001), and response (P = .012). There was increased grade ≥ 3 toxicity in arm 2 (34% v 53%; P < .001), mostly lymphopenia and fatigue. This study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.

[The characteristics of type I, III collagen and LN in pulmonary fibrosis induced by uranium ore dust in rats].

PubMed

Hu, Ying-chun; Luo, Zhen-hua; Yuan, Xing-jiang; Yang, Li-ping; Wang, Shou-feng; Li, Guang-yue; He, Xing-peng

2011-02-01

To explore the characteristics of LN and type I, III collagen in pulmonary fibrosis induced by uranium ore dust in rats. 60 adult Wistar rats were divided randomly into two groups, control group (30 rats) and uranium ore dust group (30 rats). Non-exposed intratracheal instillation method was used. Uranium ore dust group was exposed 20 mg/ml uranium ore dust suspension 1ml per rat, meanwhile control group was exposed normal saline 1ml per rat. Post-exposed the 7, 14, 21, 30 and 60 d, 6 rats in each group were killed randomly, lung tissue were collected. The pathological changes in lung tissue were observed by microscope using HE staining, the collagen I and III in lungs were observed by polarizing microscope using Biebrich scarlet staining. The expression of LN protein in lung tissue was observed by immunohistochemistry-SP. During lung fibrosis, a large amount of the proliferated I and III collagen in lungs were observed. Post-exposure to uranium ore dust, the characteristics in proliferated collagen in lungs were type I collagen deposited in lung interstitium mainly in the early stage. The area percentage of collagen I and III was increased significantly at 7, 14, 21, 30 and 60d in the experimental group as compared with that in the control group (P < 0.05 or P < 0.01). The over expression of LN in the lung tissue were observed. The expression of LN was distributed in the lung tissue as thickening of the linear or cluster. The integral optical density of LN was increased significantly at 21, 30 and 60 d in the experimental group as compared with that in the control group (P < 0.05 or P < 0.01). After exposure to uranium ore dust, the characteristics in proliferated collagen in lungs are the type of I collagen deposited in lung interstitium mainly in the early stage, while the type of III collagen increase significantly at the later period. The overexpression of LN exists in the process of pulmonary fibrosis. It suggests that LN has a role effect in the process of pulmonary fibrosis.

Pulsatile luteinizing hormone patterns in the follicular phase of the menstrual cycle, polycystic ovarian disease (PCOD) and non-PCOD secondary amenorrhea.

PubMed

Burger, C W; Korsen, T; van Kessel, H; van Dop, P A; Caron, F J; Schoemaker, J

1985-12-01

To characterize the oscillations of plasma LH in normally cycling and amenorrheic women, three groups of women were studied: I, normal women during the follicular phase of the cycle (n = 9); II, women with polycystic ovarian disease (PCOD; n = 11); and III, women with non-PCOD secondary amenorrhea (n = 12). Blood samples were obtained at 10-min intervals for 6 h on 2 separate days. A pulse was defined as an increase in LH at least 20% over the preceding lowest value (nadir). Since LHRH release immediately follows the nadir of the LH levels, the nadir interval (NI) was used for analysis. For analysis, the results from 1 day were selected at random from each subject, and from each day, the same number of NIs also were randomly selected. When two NIs from each patient were selected, the median NI was 75 min in group I, 45 min in group II, and 45 min in group III. When three or four NIs were chosen, the median NI was 60 min in group I, 50 min in group II, and 40 min in group III. The differences between the groups were statistically significant. When three NIs were selected, the mean of the corresponding LH amplitudes was 2.8 U/liter in group I, 6.0 U/liter in group II, and 1.5 U/liter in group III. The differences between these groups were statistically significant. Thus, the NI in PCOD patients was shorter than that during the follicular phase of the cycle, but this short NI is not unique for PCOD, since the NI in non-PCOD secondary amenorrhea patients was even smaller. The LH amplitude was higher in PCOD and lower in non-PCOD secondary amenorrhea compared to that during the follicular phase of the cycle. The decrease in NI in PCOD and/or non-PCOD secondary amenorrhea vs. the NI of the follicular phase could be explained by either a higher frequency of LHRH pulses from the hypothalamus or an increased sensitivity of the pituitary leading to a greater response of the pituitary to LHRH pulses.

Long Detection Programming in Single-Chamber Defibrillators Reduces Unnecessary Therapies and Mortality: The ADVANCE III Trial.

PubMed

Gasparini, Maurizio; Lunati, Maurizio G; Proclemer, Alessandro; Arenal, Angel; Kloppe, Axel; Martínez Ferrer, Josè B; Hersi, Ahmad S; Gulaj, Marcin; Wijffels, Maurits C E; Santi, Elisabetta; Manotta, Laura; Varma, Niraj

2017-11-01

This study sought to evaluate the effects of programming a long detection in single-chamber (VVI) implantable cardioverter-defibrillators (ICDs) in the multicenter prospective ADVANCE III (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III) trial. Programming strategies may reduce unnecessary ICD shocks and their adverse effects but to date have been described only for dual-chamber ICDs. A total of 545 subjects (85% male; atrial fibrillation 25%, left ventricular ejection fraction 31%, ischemic etiology 68%, secondary prevention indications 32%) receiving a VVI ICD were randomized to long detection (30 of 40 intervals) or standard programming (18 of 24 intervals) based on device type, atrial fibrillation history, and indication. In both arms, antitachycardia pacing (ATP) therapy during charging was programmed for episodes with cycle length 320 to 200 ms and shock only for cycle length <200 ms. Wavelet and stability functions enabled. Therapies delivered were compared using a negative binomial regression model. A total of 267 patients were randomized to long detection and 278 to the control group. Median follow-up was 12 months. One hundred twelve therapies (shocks and ATP) occurred in the long detection arm versus 257 in the control arm, for a 48% reduction with 30 of 40 intervals (95% confidence interval [CI]: 0.36 to 0.76; p = 0.002). In the long detection arm, overall shocks were reduced by 40% compared to the control arm (48 vs. 24; 95% CI: 0.38 to 0.94; p = 0.026) and appropriate shocks by 51% (34 vs. 74; 95% CI: 0.26 to 0.94; p = 0.033). Syncopal events did not differ between arms, but survival improved in the long detection arm. Among patients implanted with a VVI ICD, programming with the long detection interval significantly reduced appropriate therapies, shocks, and all-cause mortality. (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III [ADVANCEIII]; NCT00617175). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy

PubMed Central

Blackwell, K.; Semiglazov, V.; Krasnozhon, D.; Davidenko, I.; Nelyubina, L.; Nakov, R.; Stiegler, G.; Singh, P.; Schwebig, A.; Kramer, S.; Harbeck, N.

2015-01-01

Background Biosimilars of filgrastim are in widespread clinical use in Europe. This phase III study compares biosimilar filgrastim (EP2006), with the US-licensed reference product, Neupogen®, in breast cancer patients receiving (neo)adjuvant myelosuppressive chemotherapy (TAC). Patients and methods A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomized 1:1:1:1 into four arms. Two arms received only one product (nonalternating), biosimilar or reference, and two arms (alternating) received alternating treatments during each cycle (biosimilar then reference or vice versa). The primary end point was duration of severe neutropenia (DSN) during cycle 1. Results The baseline characteristics were balanced between the four treatment arms. Noninferiority of biosimilar versus the reference was demonstrated: DSN (days) in cycle 1 was 1.17 ± 1.11 (biosimilar, N = 101) and 1.20 ± 1.02 (reference, N = 103), 97.5% confidence interval lower boundary for the difference was −0.26 days (above the predefined limit of −1 day). No clinically meaningful differences were observed regarding any other efficacy parameter: incidence of febrile neutropenia (FN); hospitalization due to FN; incidence of infections; depth and time of absolute neutrophil count (ANC) nadir and time to ANC recovery during cycle 1 and across all cycles. The pattern and frequency of adverse events were similar across all treatments. Conclusion This study demonstrates that biosimilar and the reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially benefiting public health by increasing access to filgrastim treatment. Study number NCT01519700. PMID:26122726

Safety and feasibility of pulmonary artery pressure-guided heart failure therapy: rationale and design of the prospective CardioMEMS Monitoring Study for Heart Failure (MEMS-HF).

PubMed

Angermann, Christiane E; Assmus, Birgit; Anker, Stefan D; Brachmann, Johannes; Ertl, Georg; Köhler, Friedrich; Rosenkranz, Stephan; Tschöpe, Carsten; Adamson, Philip B; Böhm, Michael

2018-05-19

Wireless monitoring of pulmonary artery (PA) pressures with the CardioMEMS HF™ system is indicated in patients with New York Heart Association (NYHA) class III heart failure (HF). Randomized and observational trials have shown a reduction in HF-related hospitalizations and improved quality of life in patients using this device in the United States. MEMS-HF is a prospective, non-randomized, open-label, multicenter study to characterize safety and feasibility of using remote PA pressure monitoring in a real-world setting in Germany, The Netherlands and Ireland. After informed consent, adult patients with NYHA class III HF and a recent HF-related hospitalization are evaluated for suitability for permanent implantation of a CardioMEMS™ sensor. Participation in MEMS-HF is open to qualifying subjects regardless of left ventricular ejection fraction (LVEF). Patients with reduced ejection fraction must be on stable guideline-directed pharmacotherapy as tolerated. The study will enroll 230 patients in approximately 35 centers. Expected duration is 36 months (24-month enrolment plus ≥ 12-month follow-up). Primary endpoints are freedom from device/system-related complications and freedom from pressure sensor failure at 12-month post-implant. Secondary endpoints include the annualized rate of HF-related hospitalization at 12 months versus the rate over the 12 months preceding implant, and health-related quality of life. Endpoints will be evaluated using data obtained after each subject's 12-month visit. The MEMS-HF study will provide robust evidence on the clinical safety and feasibility of implementing haemodynamic monitoring as a novel disease management tool in routine out-patient care in selected European healthcare systems. ClinicalTrials.gov; NCT02693691.

Using the Saturn V and Titan III Vibroacoustic Databanks for Random Vibration Criteria Development

NASA Technical Reports Server (NTRS)

Ferbee, R C.

2009-01-01

This is an update to TN D-7159, "Development and Application of Vibroacoustic Structural Data Banks in Predicting Vibration Design and Test Criteria for Rocket Vehicle Structures", which was originally published in 1973. Errors in the original document have been corrected and additional data from the Titan III program have been included. Methods for using the vibroacoustic databanks for vibration test criteria development are shown, as well as all of the data with drawings and pictures of the measurement locations. An Excel spreadsheet with the data included is available from the author.

Dynamic evolution of Rayleigh-Taylor bubbles from sinusoidal, W-shaped, and random perturbations

NASA Astrophysics Data System (ADS)

Zhou, Zhi-Rui; Zhang, You-Sheng; Tian, Bao-Lin

2018-03-01

Implicit large eddy simulations of two-dimensional Rayleigh-Taylor instability at different density ratios (i.e., Atwood number A =0.05 , 0.5, and 0.9) are conducted to investigate the late-time dynamics of bubbles. To produce a flow field full of bounded, semibounded, and chaotic bubbles, three problems with distinct perturbations are simulated: (I) periodic sinusoidal perturbation, (II) isolated W-shaped perturbation, and (III) random short-wave perturbations. The evolution of height h , velocity v , and diameter D of the (dominant) bubble with time t are formulated and analyzed. In problem I, during the quasisteady stage, the simulations confirm Goncharov's prediction of the terminal speed v∞=Fr√{A g λ /(1 +A ) } , where Fr=1 /√{3 π } . Moreover, the diameter D at this stage is found to be proportional to the initial perturbation wavelength λ as D ≈λ . This differed from Daly's simulation result of D =λ (1 +A )/2 . In problem II, a W-shaped perturbation is designed to produce a bubble environment similar to that of chaotic bubbles in problem III. We obtain a similar terminal speed relationship as above, but Fr is replaced by Frw≈0.63 . In problem III, the simulations show that h grows quadratically with the bubble acceleration constant α ≡h /(A g t2)≈0.05 , and D expands self-similarly with a steady aspect ratio β ≡D /h ≈(1 +A )/2 , which differs from existing theories. Therefore, following the mechanism of self-similar growth, we derive a relationship of β =4 α (1 +A ) /Frw2 to relate the evolution of chaotic bubbles in problem III to that of semibounded bubbles in problem II. The validity of this relationship highlights the fact that the dynamics of chaotic bubbles in problem III are similar to the semibounded isolated bubbles in problem II, but not to that of bounded periodic bubbles in problem I.

Comparison of survival rates between 3D conformal radiotherapy and intensity-modulated radiotherapy in patients with stage III non-small cell lung cancer.

PubMed

Kong, Moonkyoo; Hong, Seong Eon

2016-01-01

Randomized trials showing a clear survival benefit of intensity-modulated radiotherapy (IMRT) over 3-dimensional conformal radiotherapy (3D-CRT) in the treatment of lung cancer are lacking. This study compared the survival rates of patients with stage III non-small cell lung cancer who were treated with either 3D-CRT or IMRT and analyzed the prognostic factors for survival. From January 2008 to July 2015, 19 patients were treated with IMRT and 30 were treated with 3D-CRT in our institution. The choice between 3D-CRT and IMRT was determined by the physician based on tumor extent and general condition of the patients. The primary endpoint of this study was overall survival. The secondary endpoints were loco-regional recurrence-free survival, distant metastasis-free survival, and the incidence of radiation-induced lung and esophageal toxicities. The 1- and 2-year overall survival rates were 94.7% and 77.1% in the IMRT group and 76.7% and 52.5% in the 3D-CRT group, respectively. The overall survival rates of the IMRT group were higher than those of the 3D-CRT group; however, these differences were not statistically significant ( P =0.072). Gross tumor volume was significantly associated with the overall survival rate. The 1- and 2-year loco-regional recurrence-free survival rates were 63.2% and 51% in the IMRT group and 67.5% and 48.1% in the 3D-CRT group ( P =0.897), respectively. The 1- and 2-year distant metastasis-free survival rates were 78.9% and 68.4% in the IMRT group and 62.6% and 40.9% in the 3D-CRT group ( P =0.120), respectively. Chemotherapy and treatment interruption were significantly associated with distant metastasis-free survival. IMRT showed comparable or better overall survival compared with 3D-CRT in patients with stage III non-small cell lung cancer. To confirm the results of this study, further randomized prospective trials comparing IMRT with 3D-CRT are warranted.

Evidence Synthesis in Harm Assessment of Medicines Using the Example of Rosiglitazone and Myocardial Infarction.

PubMed

Rietbergen, Charlotte; Stefansdottir, Gudrun; Leufkens, Hubert G; Knol, Mirjam J; De Bruin, Marie L; Klugkist, Irene

2017-01-01

The current system of harm assessment of medicines has been criticized for relying on intuitive expert judgment. There is a call for more quantitative approaches and transparency in decision-making. Illustrated with the case of cardiovascular safety concerns for rosiglitazone, we aimed to explore a structured procedure for the collection, quality assessment, and statistical modeling of safety data from observational and randomized studies. We distinguished five stages in the synthesis process. In Stage I, the general research question, population and outcome, and general inclusion and exclusion criteria are defined and a systematic search is performed. Stage II focusses on the identification of sub-questions examined in the included studies and the classification of the studies into the different categories of sub-questions. In Stage III, the quality of the identified studies is assessed. Coding and data extraction are performed in Stage IV. Finally, meta-analyses on the study results per sub-question are performed in Stage V. A Pubmed search identified 30 randomized and 14 observational studies meeting our search criteria. From these studies, we identified 4 higher level sub-questions and 4 lower level sub-questions. We were able to categorize 29 individual treatment comparisons into one or more of the sub-question categories, and selected study duration as an important covariate. We extracted covariate, outcome, and sample size information at the treatment arm level of the studies. We extracted absolute numbers of myocardial infarctions from the randomized study, and adjusted risk estimates with 95% confidence intervals from the observational studies. Overall, few events were observed in the randomized studies that were frequently of relatively short duration. The large observational studies provided more information since these were often of longer duration. A Bayesian random effects meta-analysis on these data showed no significant increase in risk of rosiglitazone for any of the sub-questions. The proposed procedure can be of additional value for drug safety assessment because it provides a stepwise approach that guides the decision-making in increasing process transparency. The procedure allows for the inclusion of results from both randomized an observational studies, which is especially relevant for this type of research.

Correlation and volatility in an Indian stock market: A random matrix approach

NASA Astrophysics Data System (ADS)

Kulkarni, Varsha; Deo, Nivedita

2007-11-01

We examine the volatility of an Indian stock market in terms of correlation of stocks and quantify the volatility using the random matrix approach. First we discuss trends observed in the pattern of stock prices in the Bombay Stock Exchange for the three-year period 2000 2002. Random matrix analysis is then applied to study the relationship between the coupling of stocks and volatility. The study uses daily returns of 70 stocks for successive time windows of length 85 days for the year 2001. We compare the properties of matrix C of correlations between price fluctuations in time regimes characterized by different volatilities. Our analyses reveal that (i) the largest (deviating) eigenvalue of C correlates highly with the volatility of the index, (ii) there is a shift in the distribution of the components of the eigenvector corresponding to the largest eigenvalue across regimes of different volatilities, (iii) the inverse participation ratio for this eigenvector anti-correlates significantly with the market fluctuations and finally, (iv) this eigenvector of C can be used to set up a Correlation Index, CI whose temporal evolution is significantly correlated with the volatility of the overall market index.

Treatment for unicameral bone cysts in long bones: an evidence based review.

PubMed

Donaldson, Sandra; Chundamala, Josie; Yandow, Suzanne; Wright, James G

2010-03-20

The purpose of this paper is to perform an evidence based review for treatment of unicameral bone cysts. A search of MEDLINE (1966 to 2009) was conducted and the studies were classified according to levels of evidence. This review includes only comparative Level I-III studies. The systematic review identified 16 studies. There is one level I study, one level II study and the remaining 14 studies are level III. Seven of the sixteen studies had statistically different results: three studies indicated that steroid injection was superior to bone marrow injection or curettage and bone grafting; one study indicated that cannulated screws were superior to steroid injections; one study indicated resection and myoplasty was superior to steroid injection; one study indicated a combination of steroid, demineralized bone matrix and bone marrow aspirate, and curettage and bone grafting were superior to steroid injection; and one study indicated that curettage and bone grafting was superior to non-operative immobilization. Based on one Level I study, including a limited number of individuals, steroid injection seems to be superior to bone marrow injection. As steroid injections have already demonstrated superiority over bone marrow injections in a randomized clinical trial, the next step would be a prospective trial comparing steroid injections with other treatments.

Treatment for unicameral bone cysts in long bones: an evidence based review

PubMed Central

Donaldson, Sandra; Chundamala, Josie; Yandow, Suzanne; Wright, James G.

2010-01-01

The purpose of this paper is to perform an evidence based review for treatment of unicameral bone cysts. A search of MEDLINE (1966 to 2009) was conducted and the studies were classified according to levels of evidence. This review includes only comparative Level I-III studies. The systematic review identified 16 studies. There is one level I study, one level II study and the remaining 14 studies are level III. Seven of the sixteen studies had statistically different results: three studies indicated that steroid injection was superior to bone marrow injection or curettage and bone grafting; one study indicated that cannulated screws were superior to steroid injections; one study indicated resection and myoplasty was superior to steroid injection; one study indicated a combination of steroid, demineralized bone matrix and bone marrow aspirate, and curettage and bone grafting were superior to steroid injection; and one study indicated that curettage and bone grafting was superior to non-operative immobilization. Based on one Level I study, including a limited number of individuals, steroid injection seems to be superior to bone marrow injection. As steroid injections have already demonstrated superiority over bone marrow injections in a randomized clinical trial, the next step would be a prospective trial comparing steroid injections with other treatments. PMID:21808696

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study

PubMed Central

Meissner, H. O.; Mscisz, A.; Reich-Bilinska, H.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Kedzia, B.; Lowicka, A.; Barchia, I.

2006-01-01

This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene’s Score (GMS) and Kupperman’s Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT). PMID:23675006

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study.

PubMed

Meissner, H O; Mscisz, A; Reich-Bilinska, H; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

2006-12-01

This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).

Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial.

PubMed

Demetri, George D; von Mehren, Margaret; Jones, Robin L; Hensley, Martee L; Schuetze, Scott M; Staddon, Arthur; Milhem, Mohammed; Elias, Anthony; Ganjoo, Kristen; Tawbi, Hussein; Van Tine, Brian A; Spira, Alexander; Dean, Andrew; Khokhar, Nushmia Z; Park, Youn Choi; Knoblauch, Roland E; Parekh, Trilok V; Maki, Robert G; Patel, Shreyaskumar R

2016-03-10

This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control-progression-free survival (PFS), time to progression, objective response rate, and duration of response-as well as safety and patient-reported symptom scoring. A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm. Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies. © 2015 by American Society of Clinical Oncology.

National randomized controlled trial of virtual house calls for Parkinson disease.

PubMed

Beck, Christopher A; Beran, Denise B; Biglan, Kevin M; Boyd, Cynthia M; Dorsey, E Ray; Schmidt, Peter N; Simone, Richard; Willis, Allison W; Galifianakis, Nicholas B; Katz, Maya; Tanner, Caroline M; Dodenhoff, Kristen; Aldred, Jason; Carter, Julie; Fraser, Andrew; Jimenez-Shahed, Joohi; Hunter, Christine; Spindler, Meredith; Reichwein, Suzanne; Mari, Zoltan; Dunlop, Becky; Morgan, John C; McLane, Dedi; Hickey, Patrick; Gauger, Lisa; Richard, Irene Hegeman; Mejia, Nicte I; Bwala, Grace; Nance, Martha; Shih, Ludy C; Singer, Carlos; Vargas-Parra, Silvia; Zadikoff, Cindy; Okon, Natalia; Feigin, Andrew; Ayan, Jean; Vaughan, Christina; Pahwa, Rajesh; Dhall, Rohit; Hassan, Anhar; DeMello, Steven; Riggare, Sara S; Wicks, Paul; Achey, Meredith A; Elson, Molly J; Goldenthal, Steven; Keenan, H Tait; Korn, Ryan; Schwarz, Heidi; Sharma, Saloni; Stevenson, E Anna; Zhu, William

2017-09-12

To determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable. In a 1-year randomized controlled trial, we compared usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes. Primary outcome measures were feasibility, as measured by the proportion who completed at least one virtual visit and the proportion of virtual visits completed on time; and efficacy, as measured by the change in the Parkinson's Disease Questionnaire-39, a quality of life scale. Secondary outcomes included quality of care, caregiver burden, and time and travel savings. A total of 927 individuals indicated interest, 210 were enrolled, and 195 were randomized. Participants had recently seen a specialist (73%) and were largely college-educated (73%) and white (96%). Ninety-five (98% of the intervention group) completed at least one virtual visit, and 91% of 388 virtual visits were completed. Quality of life did not improve in those receiving virtual house calls (0.3 points worse on a 100-point scale; 95% confidence interval [CI] -2.0 to 2.7 points; p = 0.78) nor did quality of care or caregiver burden. Each virtual house call saved patients a median of 88 minutes (95% CI 70-120; p < 0.0001) and 38 miles per visit (95% CI 36-56; p < 0.0001). Providing remote neurologic care directly into the homes of people with PD was feasible and was neither more nor less efficacious than usual in-person care. Virtual house calls generated great interest and provided substantial convenience. NCT02038959. This study provides Class III evidence that for patients with PD, virtual house calls from a neurologist are feasible and do not significantly change quality of life compared to in-person visits. The study is rated Class III because it was not possible to mask patients to visit type. © 2017 American Academy of Neurology.

Efficacy according to blind independent central review: Post-hoc analyses from the phase III, randomized, multicenter, IPASS study of first-line gefitinib versus carboplatin/paclitaxel in Asian patients with EGFR mutation-positive advanced NSCLC.

PubMed

Wu, Yi-Long; Saijo, Nagahiro; Thongprasert, Sumitra; Yang, J C-H; Han, Baohui; Margono, Benjamin; Chewaskulyong, Busayamas; Sunpaweravong, Patrapim; Ohe, Yuichiro; Ichinose, Yukito; Yang, Jin-Ji; Mok, Tony S K; Young, Helen; Haddad, Vincent; Rukazenkov, Yuri; Fukuoka, Masahiro

2017-02-01

The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC. We report post-hoc analyses of IPASS data by blind independent central review (BICR), performed at the request of the US FDA, in a subset of patients with EGFR mutation-positive NSCLC. Eligible patients (aged ≥18 years; histologically/cytologically confirmed Stage IIB/IV adenocarcinoma NSCLC; non- or former light-smokers; treatment-naïve) were randomly assigned 1:1 to gefitinib (250mg/day) or carboplatin (dose calculated to produce an area under the curve of 5 or 6 mg/mL/minute)/paclitaxel (200mg/m 2 ). Primary endpoint: PFS. BICR analyses included PFS, ORR, and duration of response (DoR). Scans from 186 IPASS patients (gefitinib n=88, carboplatin/paclitaxel n=98) with EGFR mutation-positive NSCLC were available for BICR. Consistent with investigator-assessed results, in patients with EGFR mutation-positive NSCLC: PFS (hazard ratio 0.54; 95% confidence interval [CI] 0.38, 0.79; p=0.0012) and ORR (odds ratio 3.00; 95% CI 1.63, 5.54; p=0.0004) were significantly longer with gefitinib versus carboplatin/paclitaxel. The median DoR by BICR was 9.6 months with gefitinib and 5.5 months with carboplatin/paclitaxel. BICR analysis of IPASS data support the original, investigator-assessed results. EGFR mutation-positive status remains a significant predictor of response to first-line TKI therapy. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Efficacy and safety of topical SR-T100 gel in treating actinic keratosis in Taiwan: A Phase III randomized double-blind vehicle-controlled parallel trial.

PubMed

Yang, Chao-Chun; Wong, Tak-Wah; Lee, Chih-Hung; Hong, Chien-Hui; Chang, Chung-Hsing; Lai, Feng-Jie; Lin, Shang-Hung; Chi, Ching-Chi; Lin, Tzu-Kai; Yen, Hsi; Wu, Chin-Han; Sheu, Hamm-Ming; Lan, Cheng-Che E

2018-06-01

Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p < 0.001). Severe local reactions were reported by only one subject using SR-T100. The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Effect of transcranial direct-current stimulation combined with treadmill training on balance and functional performance in children with cerebral palsy: a double-blind randomized controlled trial.

PubMed

Duarte, Natália de Almeida Carvalho; Grecco, Luanda André Collange; Galli, Manuela; Fregni, Felipe; Oliveira, Cláudia Santos

2014-01-01

Cerebral palsy refers to permanent, mutable motor development disorders stemming from a primary brain lesion, causing secondary musculoskeletal problems and limitations in activities of daily living. The aim of the present study was to determine the effects of gait training combined with transcranial direct-current stimulation over the primary motor cortex on balance and functional performance in children with cerebral palsy. A double-blind randomized controlled study was carried out with 24 children aged five to 12 years with cerebral palsy randomly allocated to two intervention groups (blocks of six and stratified based on GMFCS level (levels I-II or level III).The experimental group (12 children) was submitted to treadmill training and anodal stimulation of the primary motor cortex. The control group (12 children) was submitted to treadmill training and placebo transcranial direct-current stimulation. Training was performed in five weekly sessions for 2 weeks. Evaluations consisted of stabilometric analysis as well as the administration of the Pediatric Balance Scale and Pediatric Evaluation of Disability Inventory one week before the intervention, one week after the completion of the intervention and one month after the completion of the intervention. All patients and two examiners were blinded to the allocation of the children to the different groups. The experimental group exhibited better results in comparison to the control group with regard to anteroposterior sway (eyes open and closed; p<0.05), mediolateral sway (eyes closed; p<0.05) and the Pediatric Balance Scale both one week and one month after the completion of the protocol. Gait training on a treadmill combined with anodal stimulation of the primary motor cortex led to improvements in static balance and functional performance in children with cerebral palsy. Ensaiosclinicos.gov.br/RBR-9B5DH7.

The standardized live patient and mechanical patient models--their roles in trauma teaching.

PubMed

Ali, Jameel; Al Ahmadi, Khalid; Williams, Jack Ivan; Cherry, Robert Allen

2009-01-01

We have previously demonstrated improved medical student performance using standardized live patient models in the Trauma Evaluation and Management (TEAM) program. The trauma manikin has also been offered as an option for teaching trauma skills in this program. In this study, we compare performance using both models. Final year medical students were randomly assigned to three groups: group I (n = 22) with neither model, group II (n = 24) with patient model, and group III (n = 24) with mechanical model using the same clinical scenario. All students completed pre-TEAM and post-TEAM multiple choice question (MCQ) exams and an evaluation questionnaire scoring five items on a scale of 1 to 5 with 5 being the highest. The items were objectives were met, knowledge improved, skills improved, overall satisfaction, and course should be mandatory. Students (groups II and III) then switched models, rating preferences in six categories: more challenging, more interesting, more dynamic, more enjoyable learning, more realistic, and overall better model. Scores were analyzed by ANOVA with p < 0.05 being considered statistically significant. All groups had similar scores (means % +/- SD)in the pretest (group I - 50.8 +/- 7.4, group II - 51.3 +/- 6.4, group III - 51.1 +/- 6.6). All groups improved their post-test scores but groups II and III scored higher than group I with no difference in scores between groups II and III (group I - 77.5 +/- 3.8, group II - 84.8 +/- 3.6, group III - 86.3 +/- 3.2). The percent of students scoring 5 in the questionnaire are as follows: objectives met - 100% for all groups; knowledge improved: group I - 91%, group II - 96%, group III - 92%; skills improved: group I - 9%, group II - 83%, group III - 96%; overall satisfaction: group I - 91%, group II - 92%, group III - 92%; should be mandatory: group I - 32%, group II - 96%, group III - 100%. Student preferences (48 students) are as follows: the mechanical model was more challenging (44 of 48); more interesting (40 of 48); more dynamic (46 of 48); more enjoyable (48 of 48); more realistic (32/48), and better overall model (42 of 48). Using the TEAM program, we have demonstrated that improvement in knowledge and skills are equally enhanced by using mechanical or patient models in trauma teaching. However, students overwhelmingly preferred the mechanical model.

Cisplatin plus gemcitabine with or without vinorelbine as induction chemotherapy prior to radical locoregional treatment for patients with stage III non-small-cell lung cancer (NSCLC): results of a prospective randomized study.

PubMed

Esteban, Emilio; de Sande, Jose-Luis; Villanueva, Noemi; Corral, Norberto; Muñiz, Isabel; Vieitez, José M A; Fra, Joaquin; Fernández, Yolanda; Estrada, Enrique; Fernandez, José-Luis; Luque, Maria; Jimenez, Paula; Mareque, Beatriz; Capellan, Marta; Buesa, José M A; Lacave, Angel Jimenez

2007-02-01

To evaluate possible improvement in objective response of adding vinorelbine (V) to the combination of cisplatin/gemcitabine (CG) in induction chemotherapy for stage III NSCLC, patients (n=154) aged < or =75 years, Karnofsky index > or =70%, were stratified by stage (IIIA versus IIIB) and randomly assigned to receive: C (50mg/m(2) i.v.) plus G (1250mg/m(2) i.v.) or CG plus V (25mg/m(2) i.v.). All drugs were administered on days 1 and 8 of an every 3-week cycle. At conclusion, local treatment (LT) with surgery and/or radiotherapy was scheduled. The results indicated that, following a median of 3 cycles, the overall efficacy was 65% in the CG and 61% in the CGV group. Most patients in both groups received radiotherapy as part of their LT. Pathological complete response was confirmed by surgery in 18% in the CG and 25% in the CGV group. Median progression-free survival was 368 days in the CG and 322 days in the CGV group. There were no statistically significant differences in toxicities between groups. We conclude that the CG and CGV combinations had similar efficacy and moderate toxicity, without accruing to the triplet combination.

Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial.

PubMed

Bunnapradist, S; Ciechanowski, K; West-Thielke, P; Mulgaonkar, S; Rostaing, L; Vasudev, B; Budde, K

2013-03-01

Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4-15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges.

PubMed

Chen, Y H Joshua; Gesser, Richard; Luxembourg, Alain

2015-02-01

The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical, vulvar, vaginal, and anal cancers and related precancers caused by human papillomavirus types 6, 11, 16, and 18. These four types account for approximately 70% of cervical cancers. A nine-valent human papillomavirus vaccine, including the four original types (6, 11, 16, and 18) plus the next five most prevalent types in cervical cancer (31, 33, 45, 52, and 58) could provide approximately 90% overall cervical cancer coverage. To expedite the nine-valent human papillomavirus vaccine clinical development, an adaptive, seamless Phase IIB/III outcome trial with ∼ 15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registrations. We discuss the design rationale and implementation challenges of the outcome trial, focusing on the adaptive feature of the seamless Phase IIB/III design. Subjects were enrolled in two parts (Part A and Part B). Approximately 1240 women, 16-26 years of age, were enrolled in Part A for Phase IIB evaluation and equally randomized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine (active control). Based on an interim analysis of immunogenicity and safety, one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study. Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses. In addition, ∼ 13,400 women 16-26 years of age were enrolled in Part B, randomized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine, and followed for immunogenicity, efficacy, and safety. A seamless Phase IIB/III design was justified by the extensive pre-existing knowledge of the licensed four-valent human papillomavirus vaccine and the development objectives for the nine-valent human papillomavirus vaccine. Subjects enrolled in Part A who received either the selected nine-valent human papillomavirus formulation or four-valent human papillomavirus vaccine contributed ∼ 10% of person-years of follow-up due to its earlier start-thereby maximizing the overall efficiency of the trial. Some of the challenges encountered in the implementation of the adaptive design included practical considerations during Phase IIB formulation selection by internal and external committees, End-of-Phase II discussion with health authorities and managing changes in the assay for immunological endpoints. Application of the experience and lesson learned from this seamless adaptive design to other clinical programs may depend on case-by-case consideration. A seamless Phase IIB/III adaptive design was successfully implemented in this large outcome study. The development time of the second-generation nine-valent human papillomavirus vaccine was shortened due to improved statistical efficiency. © The Author(s) 2014.

Bearing Dislocation and Progression of Osteoarthritis After Mobile-bearing Unicompartmental Knee Arthroplasty Vary Between Asian and Western Patients: A Meta-analysis.

PubMed

Ro, Kyung-Han; Heo, Jae-Won; Lee, Dae-Hee

2018-05-01

Implant survivorship is reported to be lower and complications, particularly bearing dislocation, are reported to be more frequent in Asian than in Western patients with medial knee osteoarthritis (OA) undergoing Oxford® Phase III unicompartmental knee arthroplasty (UKA). To date, however, these complications have not been compared between these groups of patients. The purpose of this study was to perform a meta-analysis comparing the standardized incidence rates of (1) all-cause reoperation; (2) reoperation related to bearing dislocation; and (3) reoperation related to progression of lateral compartment arthritis in Asian and Western patients with medial knee OA who underwent Oxford Phase III UKA. We searched MEDLINE® (January 1, 1976, to May 31, 2017), EMBASE® (January 1, 1985, to May 31, 2017), and the Cochrane Library (January 1, 1987, to May 31, 2017) for studies that reported complications of Oxford Phase III UKAs. Studies were included if they reported reoperation rates attributable to bearing dislocation and/or progression of lateral knee OA after surgery with this implant. Twenty-seven studies were included in this systematic review and 16 studies with followups > 5 years were included in the meta-analysis. These rates were converted to standardized incidence rate (that is, reoperations per 100 observed component years) based on mean followup and number of involved knees in each study. After applying prespecified inclusion and exclusion criteria, the studies were categorized into two groups, Asian and Western, based on hospital location. Twenty-five studies, containing 3152 Asian patients and 5455 Western patients, were evaluated. Study quality was assessed by the modified Coleman Methodology score (MCMS). Although all studies were Level IV, their mean MCMS score was 66.92 (SD, 8.7; 95% confidence interval [CI], 63.5-70.3), indicating fair quality. Because the heterogeneity of all subgroup meta-analyses was high, a random-effects model was used with estimations using the restricted maximum likelihood method. There was no difference in the proportion of Asian patients versus Western patients undergoing reoperation for any cause calculated as 100 component observed years (1.022 of 3152 Asian patients; 95% CI, 0.810-1.235 versus 1.300 of 5455 Western patients; 95% CI, 1.067-1.534; odds ratio, 0.7839; 95% CI, 0.5323-1.1545; p = 0.178). The mean reoperation rate attributable to bearing dislocation per 100 observed years was higher in Asian than in Western patients (0.525; 95% CI, 0.407-0.643 versus 0.141; 95% CI, 0.116-0.166; odds ratio, 3.7378; 95% CI, 1.694-8.248; p = 0.001) Conversely, the mean reoperation rate attributable to lateral knee OA per 100 observed years was lower in Asian than in Western patients (0.093; 95% CI, 0.070-0.115 versus 0.298; 95% CI, 0.217-0.379; odds ratio, 0.3114; 95% CI, 0.0986-0.9840; p < 0.001). Although total reoperation rates did not differ in the two populations, reoperation for bearing dislocation was more likely to occur in Asian than in Western patients, whereas reoperation for lateral knee OA progression was more likely to occur in Western than in Asian patients after Oxford Phase III UKA. Although possible explanations for these findings may be hypothesized, additional randomized, prospective comparative studies are needed. However, better survival outcomes after UKA may require consideration of ethnicity and lifestyle choices in addition to traditional surgical technique and perioperative care. Level III, therapeutic study.

Comparison of efficacy and tolerance between combination therapy and monotherapy as first-line chemotherapy in elderly patients with advanced gastric cancer: Study protocol for a randomized controlled trial.

PubMed

Lee, Keun-Wook; Zang, Dae Young; Ryu, Min-Hee; Kim, Ki Hyang; Kim, Mi-Jung; Han, Hye Sook; Koh, Sung Ae; Park, Jin Hyun; Kim, Jin Won; Nam, Byung-Ho; Choi, In Sil

2017-12-01

The combination of a fluoropyrimidine [5-fluorouracil (5-FU), capecitabine, or S-1] with a platinum analog (cisplatin or oxaliplatin) is the most widely accepted first-line chemotherapy regimen for metastatic or recurrent advanced gastric cancer (AGC), based on the results of clinical trials. However, there is little evidence to guide chemotherapy for elderly patients with AGC because of under-representation of this age group in clinical trials. Thus, the aim of this study is to determine the optimal chemotherapy regimen for elderly patients with AGC by comparing the efficacies and safeties of combination therapy versus monotherapy as first-line chemotherapy. This study is a randomized, controlled, multicenter, phase III trial. A total of 246 elderly patients (≥70 years old) with metastatic or recurrent AGC who have not received previous palliative chemotherapy will be randomly allocated to a combination therapy group or a monotherapy group. Patients randomized to the combination therapy group will receive fluoropyrimidine plus platinum combination chemotherapy (capecitabine/cisplatin, S-1/cisplatin, capecitabine/oxaliplatin, or 5-FU/oxaliplatin), and those randomized to the monotherapy group will receive fluoropyrimidine monotherapy (capecitabine, S-1, or 5-FU). The primary outcome is the overall survival of patients in each treatment group. The secondary outcomes include progression-free survival, response rate, quality of life, and safety. We are conducting this pragmatic trial to determine whether elderly patients with AGC will obtain the same benefit from chemotherapy as younger patients. We expect that this study will help guide decision-making for the optimal treatment of elderly patients with AGC.

DISTRIBUTIONS OF LAKE FISHES OF THE NORTHEAST USA--III. SALMONIDAE AND ASSOCIATED COLDWATER SPECIES

EPA Science Inventory

We present distributional maps and discuss native status for fish species characteristic of coldwater lakes, sampled from 203 randomly selected lakes in the northeastern USA (New England, New York, New Jersey). Eleven coldwater fish species from four families (Salmonidae, Osmeri...

Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial.

PubMed

Muscedere, John; Maslove, David; Boyd, John Gordon; O'Callaghan, Nicole; Lamontagne, Francois; Reynolds, Steven; Albert, Martin; Hall, Rick; McGolrick, Danielle; Jiang, Xuran; Day, Andrew G

2016-09-29

Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill. This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence. The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF. The trial was registered at www.ClinicalTrials.gov on 18 November 2013. NCT01996579 .

Modified constraint-induced therapy for children with hemiplegic cerebral palsy: a randomized trial.

PubMed

Wallen, Margaret; Ziviani, Jenny; Naylor, Olivia; Evans, Ruth; Novak, Iona; Herbert, Robert D

2011-12-01

Conventional constraint-based therapies are intensive and demanding to implement, particularly for children. Modified forms of constraint-based therapies that are family-centred may be more acceptable and feasible for families of children with cerebral palsy (CP)-but require rigorous evaluation using randomized trials. The aim of this study was to determine the effects of modified constraint-induced therapy compared with intensive occupational therapy on activities of daily living and upper limb outcomes in children with hemiplegic CP. In this assessor-blinded pragmatic randomized trial, 50 children (27 males, 23 females; age range 19 mo-7 y 10 mo) with hemiplegic CP were randomized using a concealed allocation procedure to one of two 8-week interventions: intensive occupational therapy (n = 25), or modified constraint-induced therapy (n = 25). Manual Ability Classification System (MACS) levels of the participants were, level I n = 2, II n = 37, III n = 8, and level IV n = 1; Gross Motor Function Classification System (GMFCS) levels were, level I n = 33, level II n = 15, and level III n = 1. Participants were recruited through three specialist CP centres in Australia and randomized between January 2008 and April 2010. Children randomized to modified constraint-induced therapy wore a mitt on the unaffected hand for 2 hours each day, during which time the children participated in targeted therapy. The primary outcome was the Canadian Occupational Performance Measure (COPM--measured on a 10-point scale) at completion of therapy. Other outcome measures were Goal Attainment Scaling, Assisting Hand Assessment, Pediatric Motor Activity Log, Modified Ashworth Scale, Modified Tardieu Scale, and a parent questionnaire. Assessments were carried out at 10 weeks and 6 months following randomization. All participants were included in the analysis. Between-group differences for all outcomes were neither clinically important nor statistically significant. The mean difference in COPM was 0.3 (95% confidence interval [CI] -0.8 to 1.4; p=0.61) and mean difference in COPM satisfaction was 0.1 (95% CI -1.1 to 1.2; p=0.90). Minor adverse events were reported by five of the 25 participants in the modified constraint-induced therapy group and by one of the 25 in the intensive occupational therapy group. All adverse events were related to participants' lack of acceptance of therapy. Modified constraint-induced therapy is no more effective than intensive occupational therapy for improving completion of activities of daily living or upper limb function in children with hemiplegic CP. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Effect of time on tensile bond strength of resin cement bonded to dentine and low-viscosity composite.

PubMed

Duarte, Rosângela Marques; de Goes, Mario Fernando; Montes, Marcos Antonio Japiassú Resende

2006-01-01

The purpose of this study was to evaluate the tensile bond strength (TBS) of Panavia F resin cement (PF) applied on dentine pre-treated with ED Primer (ED) and Clearfil Liner Bond 2V (CLB) coated with a layer of low-viscosity composite Protect Liner F (PLF) at 10 min, 24 h and 12 months after curing. The labial surfaces of 60 bovine lower incisors were ground to obtain a flat dentine surface, allowing a demarcation of a 4.0 mm-diameter area with adhesive tape. The teeth were randomly divided in six groups; ED was applied in groups A I, A II and A III and CLB was applied, followed by PLF, in groups B I, B II and B III. A resin composite rod with a wire loop was luted directly to the prepared surface of each group with PF. The specimens of groups A I and B I were submitted to TBS test after 10 min. Groups A II and B II were submitted to TBS test after 24 h storage and groups A III and B III were submitted to TBS test after 12 months storage. Each specimen was inspected by SEM and classified according to the failure mode. Additionally, two representative specimens of each failure mode were sectioned for a composite/dentine interface SEM evaluation. No significant statistical differences were observed among the groups at 10 min and 24 h. Groups A III and B III presented the lowest TBS values (p<0.05) after 12 months storage. PF on resin-coated dentin (PLF) showed the highest TBS values and was statistically different to PF on dentine for all the groups. The fracture pattern was generally cohesive on the adhesive/hybrid layer for groups A I, A II and A III and cohesive on composite resin for B I, B II and B III. The use of a less hydrophilic self-etching system to pre-treat dentine, coating with a low-viscosity composite layer prior luting with resin cement, may provide a protection of the hybridised complex, allowing a dentine seal during the 12 months storage period.

Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type 2 diabetes mellitus.

PubMed

Kawamori, Ryuzo; Kaku, Kohei; Hanafusa, Toshiaki; Oikawa, Tatsuya; Kageyama, Shigeru; Hotta, Nigishi

2014-02-12

We investigated the efficacy and safety of repaglinide as an add-on therapy for Japanese patients with type 2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500 mg/day, mainly) in addition to diet and exercise. In the 16-week multicenter, placebo-controlled, randomized, double-blind, parallel-group trial (the phase III study), patients with type 2 diabetes mellitus with metformin monotherapy were randomly assigned to the repaglinide or placebo group. Thereafter, a 36-week, multicenter, uncontrolled, dose-titration method study was extended to a total duration of 52 weeks (the long-term study). The primary end-point of each study was a change in glycated hemoglobin (HbA1c) from baseline. After 16 weeks, mean reductions in HbA1c were significantly greater for the repaglinide group than for the placebo group (-0.98 ± 0.72% vs 0.13 ± 0.63%, P < 0.001). In the long-term study, the mean change in HbA1c was -0.76 ± 0.83%. The rate of adverse events was 60.6 and 50.0% in the repaglinide and placebo groups, respectively, in the phase III study, and 78.3% in the long-term study. Hypoglycemia was reported in 11.7, 0 and 13.3% of patients in the repaglinide group, placebo group and long-term study, respectively. Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA1c at week 16 and in a significant long-term improvement in HbA1c at the end of the study. No safety problems were noted during the concomitant use of repaglinide and metformin. These studies were registered with JapicCTI (nos. JapicCTI-101202 and JapicCTI-101203).

Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.

PubMed

Shahbazkhani, Bijan; Sadeghi, Amirsaeid; Malekzadeh, Reza; Khatavi, Fatima; Etemadi, Mehrnoosh; Kalantri, Ebrahim; Rostami-Nejad, Mohammad; Rostami, Kamran

2015-06-05

Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.

Evidence of transmission of Mycobacterium tuberculosis by random amplified polymorphic DNA (RAPD) fingerprinting in Taipei City, Taiwan.

PubMed Central

Harn, H J; Shen, K L; Ho, L I; Yu, K W; Liu, G C; Yueh, K C; Lee, J H

1997-01-01

AIMS: To determine, by strain identification of Mycobacterium tuberculosis, whether transmission has occurred between individuals or whether new strains are present. METHODS: A rapid protocol for random amplified polymorphic DNA (RAPD) analysis was developed. This protocol was applied to 64 strains of M tuberculosis that had been confirmed by culture and microbiological methods. RESULTS: There are five groups of M tuberculosis prevalent in Taipei city, Taiwan. The major types are groups I and III. Groups I and II had been prevalent until the end of last year when, according to our group analysis, they had been eradicated. However, group III was continuously present from the middle of 1995 to the middle of 1996, and group IV was present at the end of both years, which indicated that both groups were transmitted continuously. These clustered strains had demographic characteristics consistent with a finding of transmission tuberculosis. Also, there were 13 of 64 strains with unique RAPD fingerprints that were inferred to be due primarily to the reactivation of infection. In the drug resistance analysis, the major type represented included group III and part of group IV. CONCLUSIONS: Our preliminary data imply, not only that the prevalence of M tuberculosis in Taipei city is due to transmission rather than reactivation, but that drug resistance also may play a role in tuberculosis transmission. Images PMID:9378819

Identification by Random Mutagenesis of Functional Domains in KREPB5 That Differentially Affect RNA Editing between Life Cycle Stages of Trypanosoma brucei

PubMed Central

McDermott, Suzanne M.; Carnes, Jason

2015-01-01

KREPB5 is an essential component of ∼20S editosomes in Trypanosoma brucei which contains a degenerate, noncatalytic RNase III domain. To explore the function of this protein, we used a novel approach to make and screen numerous conditional null T. brucei bloodstream form cell lines that express randomly mutagenized KREPB5 alleles. We identified nine single amino acid substitutions that could not complement the conditional loss of wild-type KREPB5. Seven of these were within the RNase III domain, and two were in the C-terminal region that has no homology to known motifs. Exclusive expression of these mutated KREPB5 alleles in the absence of wild-type allele expression resulted in growth inhibition, the loss of ∼20S editosomes, and inhibition of RNA editing in BF cells. Eight of these mutations were lethal in bloodstream form parasites but not in procyclic-form parasites, showing that multiple domains function in a life cycle-dependent manner. Amino acid changes at a substantial number of positions, including up to 7 per allele, allowed complementation and thus did not block KREPB5 function. Hence, the degenerate RNase III domain and a newly identified domain are critical for KREPB5 function and have differential effects between the life cycle stages of T. brucei that differentially edit mRNAs. PMID:26370513

Study on the Effectiveness of Virtual Reality Game-Based Training on Balance and Functional Performance in Individuals with Paraplegia

PubMed Central

Khurana, Meetika; Walia, Shefali

2017-01-01

Objective: To determine whether there is any difference between virtual reality game–based balance training and real-world task-specific balance training in improving sitting balance and functional performance in individuals with paraplegia. Methods: The study was a pre test–post test experimental design. There were 30 participants (28 males, 2 females) with traumatic spinal cord injury randomly assigned to 2 groups (group A and B). The levels of spinal injury of the participants were between T6 and T12. The virtual reality game–based balance training and real-world task-specific balance training were used as interventions in groups A and B, respectively. The total duration of the intervention was 4 weeks, with a frequency of 5 times a week; each training session lasted 45 minutes. The outcome measures were modified Functional Reach Test (mFRT), t-shirt test, and the self-care component of the Spinal Cord Independence Measure–III (SCIM-III). Results: There was a significant difference for time (p = .001) and Time × Group effect (p = .001) in mFRT scores, group effect (p = .05) in t-shirt test scores, and time effect (p = .001) in the self-care component of SCIM-III. Conclusions: Virtual reality game–based training is better in improving balance and functional performance in individuals with paraplegia than real-world task-specific balance training. PMID:29339902

Evaluation of shear bond strength of orthodontic brackets bonded with nano-filled composites.

PubMed

Chalipa, Javad; Akhondi, Mohammad Sadegh Ahmad; Arab, Sepideh; Kharrazifard, Mohammad Javad; Ahmadyar, Maryam

2013-09-01

The purpose of this study was to evaluate the shear bond strength (SBS) of orthodontic brackets bonded with two types of nano-composites in comparison to a conventional orthodontic composite. Sixty extracted human first premolars were randomly divided into 3 groups each containing 20 teeth. In group I, a conventional orthodontic composite (Transbond XT) was used to bond the brackets, while two nano-composites (Filtek TM Supreme XT and AELITE Aesthetic Enamel) were used in groups II and III respectively. The teeth were stored in distilled water at 37°C for 24 hours, thermocycled in distilled water and debonded with a universal testing machine at a crosshead speed of 1 mm/min. The adhesive remnant index (ARI) was also evaluated using a stereomicroscope. AELITE Aesthetic Enamel nano-composite revealed a SBS value of 8.44±2.09 MPa, which was higher than Transbond XT (6.91±2.13) and Filtek TM Supreme XT (6.04±2.01). Statistical analysis revealed a significant difference between groups II and III (P < 0.05). No significant difference was found between groups I and III, and between groups I and II (P > 0.05). Evaluation of ARI showed that Transbond XT left fewer adhesive remains on teeth after debonding. Results of this study indicate that the aforementioned nano-composites can be successfully used for bonding orthodontic brackets.

The Acute Effect of Humic Acid on Iron Accumulation in Rats.

PubMed

Cagin, Yasir Furkan; Sahin, N; Polat, A; Erdogan, M A; Atayan, Y; Eyol, E; Bilgic, Y; Seckin, Y; Colak, C

2016-05-01

Free iron leads to the formation of pro-oxidant reactive oxygen species (ROS). Humic acids (HAs) enhance permeability of cellular wall and act as a chelator through electron transferring. This study was designed to test chelator effect of HA on iron as well as its anti-oxidant effect against the iron-induced hepatotoxicity and cardiotoxicity. The rats used were randomly divided into four groups (n = 8/group): group I (the control group); group II (the HA group), humic acid (562 mg/kg) was given over 10 days by oral gavage; group III (the iron group), iron III hydroxide polymaltose (250 mg/kg) was given over 10 days by intraperitoneal route; and group IV (the HA plus iron group), received the iron (similar to group II) plus humic acid (similar to those in groups II and III) group. Blood and two tissue samples both from liver and heart were obtained for biochemical and histopathological evaluations. Iron deposition, the iron-induced hepatotoxicity, and cardiotoxicity were demonstrated by histopathological and biochemical manner. However, no significant differences were observed in the serum biochemical values and the histopathological results among the iron and the HA plus iron groups in the liver tissue but not in the heart tissue. The protective effects of humic acid against iron-induced cardiotoxicity were shown but not against hepatotoxicity in our study.

Study on the Effectiveness of Virtual Reality Game-Based Training on Balance and Functional Performance in Individuals with Paraplegia.

PubMed

Khurana, Meetika; Walia, Shefali; Noohu, Majumi M

2017-01-01

Objective: To determine whether there is any difference between virtual reality game-based balance training and real-world task-specific balance training in improving sitting balance and functional performance in individuals with paraplegia. Methods: The study was a pre test-post test experimental design. There were 30 participants (28 males, 2 females) with traumatic spinal cord injury randomly assigned to 2 groups (group A and B). The levels of spinal injury of the participants were between T6 and T12. The virtual reality game-based balance training and real-world task-specific balance training were used as interventions in groups A and B, respectively. The total duration of the intervention was 4 weeks, with a frequency of 5 times a week; each training session lasted 45 minutes. The outcome measures were modified Functional Reach Test (mFRT), t-shirt test, and the self-care component of the Spinal Cord Independence Measure-III (SCIM-III). Results: There was a significant difference for time ( p = .001) and Time × Group effect ( p = .001) in mFRT scores, group effect ( p = .05) in t-shirt test scores, and time effect ( p = .001) in the self-care component of SCIM-III. Conclusions: Virtual reality game-based training is better in improving balance and functional performance in individuals with paraplegia than real-world task-specific balance training.

Effect of Methanolic Leaf Extract of Ocimum basilicum L. on Benzene-Induced Hematotoxicity in Mice

PubMed Central

Saha, S.; Mukhopadhyay, M. K.; Ghosh, P. D.; Nath, D.

2012-01-01

The aim of the present study was to investigate the protective role of methanolic leaf extract of Ocimum basilicum L. against benzene-induced hematotoxicity in Swiss albino mice. GC analysis and subacute toxicity level of the extract were tested. Mice were randomly divided into three groups among which II and III were exposed to benzene vapour at a dose 300 ppm × 6 hr/day × 5 days/week for 2 weeks and group I was control. Group III of this experiment was treated with the leaf methanolic extract at a dose of 100 mg/kg body weight, a dose in nontoxic range. Hematological parameters (Hb%, RBC and WBC counts), cell cycle regulatory proteins expression and DNA fragmentation analysis of bone marrow cells was performed. There was an upregulation of p53 and p21 and downregulation of levels of CDK2, CDK4, CDK6, and cyclins D1 and E in leaf extract-treated group. DNA was less fragmented in group III compared to group II (P < 0.05). The present study indicates that the secondary metabolites of O. basilicum L. methanolic leaf extract, comprising essential oil monoterpene geraniol and its oxidized form citral as major constituents, have modulatory effect in cell cycle deregulation and hematological abnormalities induced by benzene in mice. PMID:22988471

Role of Statistical Random-Effects Linear Models in Personalized Medicine.

PubMed

Diaz, Francisco J; Yeh, Hung-Wen; de Leon, Jose

2012-03-01

Some empirical studies and recent developments in pharmacokinetic theory suggest that statistical random-effects linear models are valuable tools that allow describing simultaneously patient populations as a whole and patients as individuals. This remarkable characteristic indicates that these models may be useful in the development of personalized medicine, which aims at finding treatment regimes that are appropriate for particular patients, not just appropriate for the average patient. In fact, published developments show that random-effects linear models may provide a solid theoretical framework for drug dosage individualization in chronic diseases. In particular, individualized dosages computed with these models by means of an empirical Bayesian approach may produce better results than dosages computed with some methods routinely used in therapeutic drug monitoring. This is further supported by published empirical and theoretical findings that show that random effects linear models may provide accurate representations of phase III and IV steady-state pharmacokinetic data, and may be useful for dosage computations. These models have applications in the design of clinical algorithms for drug dosage individualization in chronic diseases; in the computation of dose correction factors; computation of the minimum number of blood samples from a patient that are necessary for calculating an optimal individualized drug dosage in therapeutic drug monitoring; measure of the clinical importance of clinical, demographic, environmental or genetic covariates; study of drug-drug interactions in clinical settings; the implementation of computational tools for web-site-based evidence farming; design of pharmacogenomic studies; and in the development of a pharmacological theory of dosage individualization.

Working With Parents to Prevent Childhood Obesity: Protocol for a Primary Care-Based eHealth Study.

PubMed

Avis, Jillian Ls; Cave, Andrew L; Donaldson, Stephanie; Ellendt, Carol; Holt, Nicholas L; Jelinski, Susan; Martz, Patricia; Maximova, Katerina; Padwal, Raj; Wild, T Cameron; Ball, Geoff Dc

2015-03-25

Parents play a central role in preventing childhood obesity. There is a need for innovative, scalable, and evidence-based interventions designed to enhance parents' motivation to support and sustain healthy lifestyle behaviors in their children, which can facilitate obesity prevention. (1) Develop an online screening, brief intervention, and referral to treatment (SBIRT) eHealth tool to enhance parents' concern for, and motivation to, support children's healthy lifestyle behaviors, (2) refine the SBIRT eHealth tool by assessing end-user acceptability, satisfaction, and usability through focus groups, and (3) determine feasibility and preliminary effectiveness of the refined SBIRT eHealth tool through a randomized controlled trial. This is a three-phase, multi-method study that includes SBIRT eHealth tool development (Phase I), refinement (Phase II), and testing (Phase III). Phase I: Theoretical underpinnings of the SBIRT tool, entitled the Resource Information Program for Parents on Lifestyle and Education (RIPPLE), will be informed by concepts applied within existing interventions, and content will be based on literature regarding healthy lifestyle behaviors in children. The SBIRT platform will be developed in partnership between our research team and a third-party intervention development company. Phase II: Focus groups with parents, as well as health care professionals, researchers, and trainees in pediatrics (n=30), will explore intervention-related perceptions and preferences. Qualitative data from the focus groups will inform refinements to the aesthetics, content, structure, and function of the SBIRT. Phase III: Parents (n=200) of children-boys and girls, 5 to 17 years old-will be recruited from a primary care pediatric clinic while they await their children's clinical appointment. Parents will be randomly assigned to one of five groups-four intervention groups and one control group-as they complete the SBIRT. The randomization function is built into the tool. Parents will complete the eHealth SBIRT using a tablet that will be connected to the Internet. Subsequently, parents will be contacted via email at 1-month follow-up to assess (1) change in concern for, and motivation to, support children's dietary and physical activity behaviors (primary outcome), and (2) use of online resources and referrals to health services for obesity prevention (secondary outcome). This research was successfully funded and received ethics approval. Development of the SBIRT started in summer 2012, and we expect all study-related activities to be completed by fall 2016. The proposed research is timely and applies a novel, technology-based application designed to enhance parents concern for, and motivation to, support children's healthy lifestyle behaviors and encourage use of online resources and community services for childhood obesity prevention. Overall, this research builds on a foundation of evidence supporting the application of SBIRTs to encourage or "nudge" individuals to make healthy lifestyle choices. Findings from Phase III of this project will directly inform a cluster randomized controlled trial to study the effectiveness of our intervention across multiple primary care-based settings. ClinicalTrials.gov NCT02330588; http://clinicaltrials.gov/ct2/show/NCT02330588 (Archived by WebCite at http://www.webcitation.org/6WyUOeRlr).

Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review.

PubMed

Strojan, Primož; Vermorken, Jan B; Beitler, Jonathan J; Saba, Nabil F; Haigentz, Missak; Bossi, Paolo; Worden, Francis P; Langendijk, Johannes A; Eisbruch, Avraham; Mendenhall, William M; Lee, Anne W M; Harrison, Louis B; Bradford, Carol R; Smee, Robert; Silver, Carl E; Rinaldo, Alessandra; Ferlito, Alfio

2016-04-01

The optimal cumulative dose and timing of cisplatin administration in various concurrent chemoradiotherapy protocols for nonmetastatic head and neck squamous cell carcinoma (HNSCC) has not been determined. The absolute survival benefit at 5 years of concurrent chemoradiotherapy protocols versus radiotherapy alone observed in prospective randomized trials reporting on the use of cisplatin monochemotherapy for nonnasopharyngeal HNSCC was extracted. In the case of nonrandomized studies, the outcome results at 2 years were compared between groups of patients receiving different cumulative cisplatin doses. Eleven randomized trials and 7 nonrandomized studies were identified. In 6 definitive radiotherapy phase III trials, a statistically significant association (p = .027) between cumulative cisplatin dose, independent of the schedule, and overall survival benefit was observed for higher doses. Results support the conclusion that the cumulative dose of cisplatin in concurrent chemoradiation protocols for HNSCC has a significant positive correlation with survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2151-E2158, 2016. © 2015 Wiley Periodicals, Inc.

Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial.

PubMed

Skorupski, K A; Uhl, J M; Szivek, A; Allstadt Frazier, S D; Rebhun, R B; Rodriguez, C O

2016-03-01

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. © 2013 John Wiley & Sons Ltd.

Failure and recovery in dynamical networks.

PubMed

Böttcher, L; Luković, M; Nagler, J; Havlin, S; Herrmann, H J

2017-02-03

Failure, damage spread and recovery crucially underlie many spatially embedded networked systems ranging from transportation structures to the human body. Here we study the interplay between spontaneous damage, induced failure and recovery in both embedded and non-embedded networks. In our model the network's components follow three realistic processes that capture these features: (i) spontaneous failure of a component independent of the neighborhood (internal failure), (ii) failure induced by failed neighboring nodes (external failure) and (iii) spontaneous recovery of a component. We identify a metastable domain in the global network phase diagram spanned by the model's control parameters where dramatic hysteresis effects and random switching between two coexisting states are observed. This dynamics depends on the characteristic link length of the embedded system. For the Euclidean lattice in particular, hysteresis and switching only occur in an extremely narrow region of the parameter space compared to random networks. We develop a unifying theory which links the dynamics of our model to contact processes. Our unifying framework may help to better understand controllability in spatially embedded and random networks where spontaneous recovery of components can mitigate spontaneous failure and damage spread in dynamical networks.

Ethical Issues for Control-Arm Patients After Revelation of Benefits of Experimental Therapy: A Framework Modeled in Neuroblastoma

PubMed Central

Unguru, Yoram; Joffe, Steven; Fernandez, Conrad V.; Yu, Alice L.

2013-01-01

In 2009, the Children's Oncology Group (COG) phase III randomized controlled trial, ANBL0032, found that adding immunotherapy (Ch14.18) to standard therapy significantly improved outcomes in patients with high-risk neuroblastoma when administered within 110 days after autologous stem-cell transplantation (SCT). After careful deliberation and consultation, the COG Neuroblastoma Committee decided to offer Ch14.18 to prior trial participants who had been randomly assigned to the control arm (no immunotherapy), regardless of the time that had elapsed since SCT. This decision occurred in the context of a limited supply of Ch14.18 and no data regarding its role when administered beyond 110 days. In this article, we analyze the numerous ethical challenges highlighted by the ANBL0032 trial, including the limits of researchers' reciprocity-based obligations to study participants, post-trial access to beneficial therapies, and the balance between scientific knowledge and parental hope. These deliberations may be useful to other researchers when considering their ethical obligations to control-arm participants in the wake of a positive randomized trial. PMID:23295797

Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

PubMed Central

Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

2010-01-01

Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

MMX Multi Matrix System mesalazine for the induction of remission in patients with mild-to-moderate ulcerative colitis: a combined analysis of two randomized, double-blind, placebo-controlled trials.

PubMed

Sandborn, W J; Kamm, M A; Lichtenstein, G R; Lyne, A; Butler, T; Joseph, R E

2007-07-15

MMX mesalazine [LIALDA (US), MEZAVANT XL (UK and Ireland) MEZAVANT (elsewhere)] utilizes MMX Multi Matrix System (MMX) technology which delivers mesalazine throughout the colon. Two phase III studies have already evaluated MMX mesalazine in patients with active, mild-to-moderate ulcerative colitis. Aim To provide more precise estimates of the efficacy of MMX mesalazine over placebo by combining the patient populations from the two phase III studies. Methods Combined data from two 8-week, double-blind, placebo-controlled trials were analyzed. Patients randomized to MMX mesalazine 2.4 g/day (once daily or 1.2 g twice daily), 4.8 g/day (once daily) or placebo were reviewed. The primary end point was clinical and endoscopic remission (modified Ulcerative Colitis-Disease Activity Index of /=1-point reduction in sigmoidoscopy score from week 0). Results Data from 517 patients were analysed. 8-week remission rates were 37.2% and 35.1% in the MMX mesalazine 2.4 g/day and 4.8 g/day groups, vs. 17.5% on placebo (P < 0.001, both comparisons). 8-week complete mucosal healing rates were 32% in both MMX mesalazine groups compared with 16% on placebo. Adverse event frequency was similar in all groups. Conclusion MMX mesalazine is effective and generally well tolerated for inducing clinical and endoscopic remission of active, mild-to-moderate ulcerative colitis.

Prevalence of metabolic syndrome in 8–18-year-old school-going children of Srinagar city of Kashmir India

PubMed Central

Andrabi, Syed M.S.; Bhat, Mohd H.; Andrabi, Syed R.S.; Kamili, Mohd M.A.; Imran, Ali; Nisar, Iqra; Nisar, Umara

2013-01-01

Aim: Obesity is the most common cause of insulin resistance and metabolic syndrome (MS). These are the most important risk factors for coronary heart disease (CHD). No evidence exists regarding the prevalence of the MS in children in sSrinagar city of Kashmir India. We aimed to evaluate the prevalence of MS in 8–18-year-old school-going children of Kashmir, India. Materials and Methods: In this cross-sectional study, 758 respondents in 8–18 years of age were randomly selected using a simple random sampling method. The self-designed questionnaire was individually completed after receiving a written informed consent. The weight, height, waist circumference (WC), body mass index (BMI), and blood pressure were measured using standard tools. Ten milliliters of blood was taken for measuring lipid profile and fasting blood sugar (FBS) of the school children. We determined MS according to the modified Adult Treatment Panel III (ATP III) criteria. Results: The prevalence of the MS was 3.8% (boys: 3.9%, girls: 3.8%) and the prevalence of obesity was 9.9% (boys: 9.9%, girls: 10.6%) among the studied children. Obese subjects had the highest proportion of MS compared with those at risk for overweight and those with normal weight (30.7% vs. 2.5% and 0.5%, respectively; P = 0.000). Conclusion: The MS is prevalent even in young children, so we suggest screening programs for children aged 8–18 years to control obesity and MS in the developing world. PMID:23776859

Risk of developing pneumonia is enhanced by the combined traits of fluoroquinolone resistance and type III secretion virulence in respiratory isolates of Pseudomonas aeruginosa.

PubMed

Sullivan, Eva; Bensman, Joyce; Lou, Mimi; Agnello, Melissa; Shriner, Kimberly; Wong-Beringer, Annie

2014-01-01

To determine the differential association of host characteristics, antimicrobial resistance, and type III secretion system virulence of Pseudomonas aeruginosa isolates with respiratory syndromes in hospitalized adult patients. Retrospective, cohort study. Community teaching hospital. Two hundred eighteen consecutive adult patients with respiratory culture positive for P. aeruginosa between January 2005 to January 2010. Medical charts were reviewed to obtain demographic, laboratory, radiographic, and clinical information. Isolates were assayed by polymerase chain reaction for genes encoding the type III secretion system effectors (ExoU, ExoS, and PcrV) and for strain relatedness using randomly amplified polymorphic DNA analysis. Levofloxacin susceptibility was determined by broth microdilution. Patients were grouped by colonization, bronchitis, or pneumonia and were compared for differential risk of developing the clinical syndrome with respect to host and microbial characteristics. Half of the study cohort (54%, 117 of 218) had pneumonia, 32% (70 of 218) had bronchitis, and 14% (31 of 218) had colonization; in-hospital mortality was 35%, 11%, and 0%, respectively. Host factors strongly associated with pneumonia development were residence in long-term care facility, healthcare-associated acquisition of P. aeruginosa, higher Acute Physiology and Chronic Health Evaluation II score, presence of enteral feeding tube, mechanical ventilation, and recent history of pneumonia. Fluoroquinolone-resistant (57% vs 34%, 16%; p < 0.0001) and multidrug-resistant (36% vs 26%, 7%; p = 0.0045) strains were more likely to cause pneumonia than bronchitis or colonization, respectively. Analysis of host and microbial factors in a multivariate regression model yielded the combined traits of fluoroquinolone resistance and gene encoding the type III secretion system ExoU effector in P. aeruginosa as the single most significant predictor of pneumonia development. These results suggest that fluoroquinolone-resistant phenotype in a type III secretion system exoU strain background contributes toward the pathogenesis of P. aeruginosa in pneumonia.

Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.

PubMed

Rascol, Olivier; Azulay, Jean-Philippe; Blin, Olivier; Bonnet, Anne-Marie; Brefel-Courbon, Christine; Césaro, Pierre; Damier, Philippe; Debilly, Bérengère; Durif, Frank; Galitzky, Monique; Grouin, Jean-Marie; Pennaforte, Sylvie; Villafane, Gabriel; Yaici, Sadek; Agid, Yves

2010-02-15

S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single-dose double-blind double-placebo 3 x 3 cross-over study. Optimal tested doses were determined during a previous open-label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (Delta UPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 +/- 8 years, PD duration: 12 +/- 6 years, UPDRS III OFF: 37 +/- 15) participated. S90049 was superior to placebo on Delta UPDRS III (-13 +/- 12 versus -7 +/- 9 respectively; estimated difference -5.2, 95% Confidence Interval (CI)[-10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, Delta UPDRS III was similar on S90049 (-21.2 +/- 10.1) and apomorphine (-23.6 +/- 14.1) (estimated difference: 4.0 95% CI [-2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. (c) 2009 Movement Disorder Society.

A randomized, double-blind, placebo-controlled trial of safinamide as add-on therapy in early Parkinson's disease patients.

PubMed

Stocchi, Fabrizio; Borgohain, Rupam; Onofrj, Marco; Schapira, Anthony H V; Bhatt, Mohit; Lucini, Valentina; Giuliani, Rodolfo; Anand, Ravi

2012-01-01

Safinamide is an α-aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add-on to dopamine agonist (DA) therapy in early-stage PD. In this 24-week, double-blind study, patients with early PD receiving a stable dose of a single DA were randomized to once-daily safinamide 100 mg, safinamide 200 mg, or placebo. The primary efficacy variable was UPDRS part III (motor examination) total score. Analysis was hierarchical: 200 mg of safinamide versus placebo was tested first; the success of safinamide 100 mg versus placebo was contingent on this. Two hundred sixty-nine patients received safinamide 100 mg (n = 90), safinamide 200 mg (n = 89), or placebo (n = 90); 70, 81, and 81 patients, respectively, completed the study. Mean improvements from baseline to week 24 in UPDRS III total scores were -3.90 for safinamide 200 mg, -6.0 for safinamide 100 mg and -3.60 for placebo. The difference between safinamide 200 mg and placebo was not significant [point estimate: -0.4; 95% confidence interval (CI): -2.3-1.4; P = 0.6504]. Although the difference between 100 mg/day and placebo was significant (point estimate: -1.9; 95% CI: -3.7 to -0.1; P = 0.0419), these results are considered exploratory. No clinically meaningful differences from placebo were observed for any safety variables. This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day. Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation. Copyright © 2011 Movement Disorder Society.

Level of clinical evidence presented at the International Society for Hip Arthroscopy Annual Scientific Meeting over 5 years (2010–2014)

PubMed Central

Kay, Jeffrey; de SA, Darren; Shallow, Scott; Simunovic, Nicole; Safran, Marc R.; Philippon, Marc J.; Ayeni, Olufemi R.

2015-01-01

The International Society for Hip Arthroscopy (ISHA) Annual Scientific Meeting is at the forefront of informing today’s orthopaedic surgeons and society of the rapid advances in the exponentially growing field of hip arthroscopy. The purpose of this study was to evaluate and observe any trends in the level of clinical evidence in the papers and posters presented at the ISHA Annual Scientific Meeting from 2010 to 2014. The online abstracts of the paper and poster presentations presented at the ISHA Annual Scientific Meetings were independently evaluated by two reviewers (582 total resulting presentations). Two reviewers screened these results for clinical studies and graded the quality of evidence from level I (i.e. randomized trials) to IV (i.e. case series) based on the American Academy of Orthopaedic Surgeons classification system. Four hundred and twenty-eight presentations met the inclusion criteria and were evaluated. Overall, 10.1% of the presentations were level I, 12.8% were level II, 30.1% were level III and 47.0% were level IV evidence. Over time, from 2010 to 2014, we observed an increase in the percentage of level II paper presentations, an increase in the proportion of level III poster presentations, and a decrease in the proportion of both level IV paper and poster presentations. Significant non-random improvement in the level of evidence presented was noted for the poster presentations (P = 0.012) but not for the paper presentations (P = 0.61) over the study period. Statistical trends demonstrate ISHA’s increased awareness and commitment to presenting higher quality evidence as the availability of this evidence increases. PMID:27011857

Transdermal granisetron for the prevention of nausea and vomiting following moderately or highly emetogenic chemotherapy in Chinese patients: a randomized, double-blind, phase III study.

PubMed

Yang, Liu-Qing; Sun, Xin-Chen; Qin, Shu-Kui; Chen, Ying-Xia; Zhang, He-Long; Cheng, Ying; Chen, Zhen-Dong; Shi, Jian-Hua; Wu, Qiong; Bai, Yu-Xian; Han, Bao-Hui; Liu, Wei; Ouyang, Xue-Nong; Liu, Ji-Wei; Zhang, Zhi-Hui; Li, Yong-Qiang; Xu, Jian-Ming; Yu, Shi-Ying

2016-12-01

The granisetron transdermal delivery system (GTDS) has been demonstrated effectiveness in the control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of GTDS in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in China. A total of 313 patients were randomized into the GTDS group (one transdermal granisetron patch, 7 days) or the oral granisetron group (granisetron oral 2 mg/day, ≥2 days). The primary endpoint was the percentage of patients achieving complete control (CC) from chemotherapy initiation until 24 h after final administration (PEEP). Chi-square test and Fisher's exact test were used for statistical analysis. Two hundred eighty-one patients were included in the per protocol analysis. During PEEP, CC was achieved by 67 (47.52%) patients in the GTDS group and 83 (59.29%) patients in the oral granisetron group. There was no statistical significance between the groups (P=0.0559). However, the difference of the CC percentage mainly occurred on the first day of chemotherapy between the groups. The CC was 70.13% on day 1 in the GTDS group, which was significantly lower than that of 91.03% in the oral granisetron group in the full analysis set. In the following days of chemotherapy, the CC was similar between the groups. In terms of cisplatin-contained regimen and female, there was statistical significance between the groups. Both treatments were well tolerated and safe. The most common adverse event was constipation. GTDS provided effective and well-tolerated control of CINV in Chinese patients, especially to non-cisplatin-contained regimen.

Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study).

PubMed

Zaanan, Aziz; Samalin, Emmanuelle; Aparicio, Thomas; Bouche, Olivier; Laurent-Puig, Pierre; Manfredi, Sylvain; Michel, Pierre; Monterymard, Carole; Moreau, Marie; Rougier, Philippe; Tougeron, David; Taieb, Julien; Louvet, Christophe

2018-04-01

In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m 2  q3w) to cisplatin (75 mg/m 2  q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated. GASTFOX study is a randomized phase III trial comparing FOLFOX alone or with docetaxel at 50 mg/m 2 (TFOX regimen) in first-line treatment for advanced gastric cancer. In both arms, cycle is repeated every 2 weeks until disease progression or unacceptable toxicity. Main eligibility criteria: histologically proven locally advanced or metastatic gastric or esogastric junction adenocarcinoma, HER negative status, measurable disease, ECOG performance status 0 or 1, and adequate renal, hepatic and bone marrow functions. The primary endpoint is radiological/clinical progression-free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (HR = 0.73) Based on a two-sided α risk of 5% and a power of 90%, 454 events are required to show this difference. Secondary endpoints included overall survival, overall response rate, safety, quality of life and the therapeutic index. This study is planned to include 506 patients to demonstrate the superiority of TFOX over FOLFOX in first-line advanced gastric cancer treatment (NCT03006432). Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial.

PubMed

Bolli, Roberto; Hare, Joshua M; Henry, Timothy D; Lenneman, Carrie G; March, Keith L; Miller, Kathy; Pepine, Carl J; Perin, Emerson C; Traverse, Jay H; Willerson, James T; Yang, Phillip C; Gee, Adrian P; Lima, João A; Moyé, Lem; Vojvodic, Rachel W; Sayre, Shelly L; Bettencourt, Judy; Cohen, Michelle; Ebert, Ray F; Simari, Robert D

2018-07-01

SENECA (StEm cell iNjECtion in cAncer survivors) is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allogeneic mesenchymal stromal cells (allo-MSCs) transendocardially in subjects with anthracycline-induced cardiomyopathy (AIC). AIC is an incurable and often fatal syndrome, with a prognosis worse than that of ischemic or nonischemic cardiomyopathy. Recently, cell therapy with MSCs has emerged as a promising new approach to repair damaged myocardium. The study population is 36 cancer survivors with a diagnosis of AIC, left ventricular (LV) ejection fraction ≤40%, and symptoms of heart failure (NYHA class II-III) on optimally-tolerated medical therapy. Subjects must be clinically free of cancer for at least two years with a ≤ 30% estimated five-year risk of recurrence. The first six subjects participated in an open-label, lead-in phase and received 100 million allo-MSCs; the remaining 30 will be randomized 1:1 to receive allo-MSCs or vehicle via 20 transendocardial injections. Efficacy measures (obtained at baseline, 6 months, and 12 months) include MRI evaluation of LV function, LV volumes, fibrosis, and scar burden; assessment of exercise tolerance (six-minute walk test) and quality of life (Minnesota Living with Heart Failure Questionnaire); clinical outcomes (MACE and cumulative days alive and out of hospital); and biomarkers of heart failure (NT-proBNP). This is the first clinical trial using direct cardiac injection of cells for the treatment of AIC. If administration of allo-MSCs is found feasible and safe, SENECA will pave the way for larger phase II/III studies with therapeutic efficacy as the primary outcome. Copyright © 2018. Published by Elsevier Inc.

Bitopertin in Negative Symptoms of Schizophrenia-Results From the Phase III FlashLyte and DayLyte Studies.

PubMed

Bugarski-Kirola, Dragana; Blaettler, Thomas; Arango, Celso; Fleischhacker, Wolfgang W; Garibaldi, George; Wang, Alice; Dixon, Mark; Bressan, Rodrigo A; Nasrallah, Henry; Lawrie, Stephen; Napieralski, Julie; Ochi-Lohmann, Tania; Reid, Carol; Marder, Stephen R

2017-07-01

There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising. Three (SunLyte [WN25308], DayLyte [WN25309], and FlashLyte [NN25310]) phase III, multicenter, randomized, 24-week, double-blind, parallel-group, placebo-controlled studies evaluated the efficacy and safety of adjunctive bitopertin in stable patients with persistent predominant negative symptoms of schizophrenia treated with antipsychotics. SunLyte met the prespecified criteria for lack of efficacy and was declared futile. Key inclusion criteria were age ≥18 years, DSM-IV-TR diagnosis of schizophrenia, score ≥40 on the sum of the 14 Positive and Negative Syndrome Scale negative symptoms and disorganized thought factors, unaltered antipsychotic treatment, and clinical stability. Following a 4-week prospective stabilization period, patients were randomly assigned 1:1:1 to bitopertin (5 mg and 10 mg [DayLyte] and 10 mg and 20 mg [FlashLyte]) or placebo once daily for 24 weeks. The primary efficacy end point was mean change from baseline in Positive and Negative Syndrome Scale negative symptom factor score at week 24. The intent-to-treat population in DayLyte and FlashLyte included 605 and 594 patients, respectively. At week 24, mean change from baseline showed improvement in all treatment arms but no statistically significant separation from placebo in Positive and Negative Syndrome Scale negative symptom factor score and all other end points. Bitopertin was well tolerated. These studies provide no evidence for superior efficacy of adjunctive bitopertin in any of the doses tested over placebo in patients with persistent predominant negative symptoms of schizophrenia. Copyright © 2017. Published by Elsevier Inc.

Impact of explained v. unexplained front-of-package nutrition labels on parent and child food choices: a randomized trial.

PubMed

Graham, Dan J; Lucas-Thompson, Rachel G; Mueller, Megan P; Jaeb, Melanie; Harnack, Lisa

2017-04-01

The present study investigated whether parent/child pairs would select more healthful foods when: (i) products were labelled with front-of-package (FOP) nutrition labels relative to packages without labels; (ii) products were labelled with colour-coded Multiple Traffic Light (MTL) FOP labels relative to monochromatic Facts up Front (FuF) FOP labels; and (iii) FOP labels were explained via in-aisle signage v. unexplained. Participants were randomly assigned to one of five conditions: (i) FuF labels with in-aisle signs explaining the labels; (ii) FuF labels, no signage; (iii) MTL labels with in-aisle signage; (iv) MTL labels, no signage; (v) control group, no labels/signage. Saturated fat, sodium, sugar and energy (calorie) content were compared across conditions. The study took place in a laboratory grocery aisle. Parent/child pairs (n 153) completed the study. Results did not support the hypothesis that MTL labels would lead to more healthful choices than FuF labels. The presence of FOP labels did little to improve the healthfulness of selected foods, with few exceptions (participants with v. without access to FOP labels selected lower-calorie cereals, participants with access to both FOP labels and in-aisle explanatory signage selected products with less saturated fat v. participants without explanatory signage). Neither MTL nor FuF FOP labels led to food choices with significantly lower saturated fat, sodium or sugar. In-aisle signs explaining the FOP labels were somewhat helpful to consumers in making more healthful dietary decisions. New FOP labelling programmes could benefit from campaigns to increase consumer awareness and understanding of the labels.

A comparative study to check fracture strength of provisional fixed partial dentures made of autopolymerizing polymethylmethacrylate resin reinforced with different materials: An in vitro study.

PubMed

Gupt, Parikshit; Nagpal, Archana; Samra, Rupandeep Kaur; Verma, Ramit; Kaur, Jasjeet; Abrol, Surbhi

2017-01-01

The purpose of the study was to evaluate the fracture strength of provisional fixed partial dentures made of autopolymerizing polymethylmethacrylate (PMMA) resin using different types of reinforcement materials to determine the best among them. Fifty samples were made (10 samples for each group) with autopolymerizing PMMA resin using reinforcement materials (stainless steel wire: looped and unlooped and glass fiber: loose and unidirectional) as 3-unit posterior bridge. The test specimens were divided into five groups depending on the reinforcing material as Group I, II, III, IV, and V; Group I: PMMA unreinforced (control group), Group II: PMMA reinforced with stainless steel wire (straight ends), Group III: PMMA reinforced with stainless steel wire (looped ends), Group IV: PMMA reinforced with unidirectional glass fibers, and Group V: PMMA reinforced with randomly distributed glass fibers. Universal testing machine was used to evaluate and compare the fracture strength of samples. Comparison of mean ultimate force and ultimate stress was done employing one-way analysis of variance and Tukey's post hoc tests. The highest and lowest mean ultimate force and mean ultimate stress were of Group IV and I, respectively. Tukey's post hoc honestly significant difference multiple comparison for mean ultimate force and stress shows the increase in strength to be statistically significant ( P < 0.05) except for the samples reinforced with randomly distributed glass fibers ( P > 0.05). Unidirectional glass fibers showed the maximum strength, which was comparable to mean values of both stainless steel wire groups. Low cost and easy technique of using stainless steel wire make it the material of choice over the unidirectional glass fiber for reinforcement in nonesthetic areas where high strength is required.

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

PubMed

Togsverd-Bo, K; Halldin, C; Sandberg, C; Gonzalez, H; Wennberg, A M; Sørensen, S S; Wulf, H C; Haedersdal, M

2018-04-01

Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions. © 2017 British Association of Dermatologists.

Corrective shoes and inserts as treatment for flexible flatfoot in infants and children.

PubMed

Wenger, D R; Mauldin, D; Speck, G; Morgan, D; Lieber, R L

1989-07-01

We performed a prospective study to determine whether flexible flatfoot in children can be influenced by treatment. One hundred and twenty-nine children who had been referred by pediatricians, and for whom the radiographic findings met the criteria for flatfoot, were randomly assigned to one of four groups: Group I, controls; Group II, treatment with corrective orthopaedic shoes; Group III, treatment with a Helfet heel-cup; or Group IV, treatment with a custom-molded plastic insert. All of the patients in Groups II, III, and IV had a minimum of three years of treatment, and ninety-eight patients whose compliance with the protocol was documented completed the study. Analysis of radiographs before treatment and at the most recent follow-up demonstrated a significant improvement in all groups (p less than 0.01), including the controls, and no significant difference between the controls and the treated patients (p greater than 0.4). We concluded that wearing corrective shoes or inserts for three years does not influence the course of flexible flatfoot in children.

The hepatoprotective role of Silymarin in isoniazid induced liver damage of rabbits.

PubMed

Jahan, Sarwat; Khan, Moosa; Imran, Sana; Sair, Mohammad

2015-06-01

To evaluate the hepatoprotective role of Silymarin against isonicotinylhydrazine-induced hepatotoxicity in rabbit model. The experimental animal study was held at Jinnah Postgraduate Medical Centre, Karachi, from April to September 2013 and comprised rabbits weighing 1-1.5kgof either gender. The animals were divided randomly into equal groups: group I underwent liver function test without any drug; in group II effects of Silymarin (50mg/kg/day orally) was observed; in group III isoniazid (50mg/kg/dayorally) was administered; and in group IV combined effects of isoniazid and silymarin were observed. Liver function tests were performed at day0 and after the treatment at day19. SPSS 16 was used for statistical analysis. The 28 rabbits in the study were divided in four groups of 7(25%) each. No mortality was recorded in any group. In group III, bilirubin level was increased and alanine transaminase was decreased significantly (p<0.05 each). In group IV, there was significant improvement in serum billirubin and serum alanine transaminase (p<0.05 each). Isonicotinylhydrazine-induced hepatotoxicity was well treated by concurrent administration of Silymarin.

The renal excretion and retention of macromolecules: The chemical structure effect.

PubMed

Rypácek, F; Drobník, J; Chmelar, V; Kálal, J

1982-01-01

Five derivatives of polyaspartamide were used as macromolecular models to study the effect of chemical structure of macromolecules on their renal excretion and retention. The parent polymer was formed solely by N(2-hydroxyethyl)aspartamide units (I) and in its derivatives about 20% of 2-hydroxyethyl groups were randomly replaced by either n-butyl- (II), 2(4-hydroxyphenyl)ethyl- (III, N- dimethylamino propyl- (IV) or the aspartamide unit was modified to free aspartic acid carboxyl (V). The rate of clearance from the serum, the deposition in the kidney tissue in comparison with the deposition in reticuloendothelial system organs-liver and spleen, as well as tissue and cellular localisation of deposits were studied on rabbits and mice taking advantage of fluorescence labelling. The clearance of macromolecular models from the serum compartment by the glomerular filtration is mainly molecular weight controlled, while the retention of macromolecules possessing the same molecular weight by the kidney tubular epithelium is strongly affected chemical modification. About thirty and hundred times higher retentions due to reabsorption in proximal tubule were found with macromolecular models II and III respectively.

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results.

PubMed

Yang, Xiaohong; Lee, Sang-Rok; Choi, Yun-Seok; Alexander, Veronica J; Digenio, Andres; Yang, Qingqing; Miller, Yury I; Witztum, Joseph L; Tsimikas, Sotirios

2016-04-01

Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.0+ antisense drug that targets apoC3 mRNA in patients with hypertriglyceridemia, including familial chylomicronemia syndrome (n = 3), volanesorsen monotherapy (n = 51), and as add-on to fibrate (n = 26), treated for 85 days and followed for 176 days. Compared with placebo, volanesorsen was associated with an 82.3 ± 11.7%, 81.3 ± 15.7%, and 80.8 ± 13.6% reduction in apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoA-I, respectively (300 mg dose;P< 0.001 for all), at day 92. Strong correlations in all assay measures were noted with total plasma apoC-III, chylomicron-apoC-III, and VLDL-apoC-III. In conclusion, novel high-throughput ELISAs were developed to detect lipoprotein-associated apoC-III, including for the first time on Lp(a). Volanesorsen uniformly lowers apoC-III on apoB-100, Lp(a), and apoA-I lipoproteins, and may be a potent agent to reduce triglycerides and cardiovascular risk mediated by apoC-III. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Variability in triactinomyxon production from Tubifex tubifex populations from the same mitochondrial DNA lineage infected with Myxobolus cerebralis, the causative agent of whirling disease in salmonids

USGS Publications Warehouse

Rasmussen, C.; Zickovich, J.; Winton, J.R.; Kerans, B.L.

2008-01-01

Myxobolus cerebralis, the causative agent of whirling disease, infects both salmonid fish and an aquatic oligochaete, Tubifex tubifex. Although M. cerebralis has been detected in river drainages throughout the United States, disease severity among wild fish populations has been highly variable. Tubifex tubifex populations have been genetically characterized using sequences from the 16S mitochondrial DNA (mtDNA) gene, the 18S ribosomal RNA gene, the internal transcribed spacer region 1 (ITS1), and randomly amplified polymorphic DNA (RAPD). Our earlier work indicated that large differences in compatibility between the parasite and populations of T. tubifex may play a substantial role in the distribution of whirling disease and resulting mortality in different watersheds. In the present study, we examined 4 laboratory populations of T. tubifex belonging to 16S mtDNA lineage III and 1 population belonging to 16S mtDNA lineage I for triactinomyxon (TAM) production after infection with M. cerebralis myxospores. All 4 16S mtDNA lineage III populations produced TAMs, but statistically significant differences in TAM production were observed. Most individuals in the 16S mtDNA lineage III-infected populations produced TAMs. The 16S mtDNA lineage I population produced few TAMs. Further genetic characterization of the 16S mtDNA lineage III populations with RAPD markers indicated that populations producing similar levels of TAMs had more genetic similarity. ?? American Society of Parasitologists 2008.

Renoprotective Effect of Humic Acid on Renal Ischemia-Reperfusion Injury: An Experimental Study in Rats.

PubMed

Akbas, Alpaslan; Silan, Coskun; Gulpinar, Murat Tolga; Sancak, Eyup Burak; Ozkanli, Sidika Seyma; Cakir, Dilek Ulker

2015-12-01

Humic acid is an antioxidant molecule used in agriculture and livestock breeding, as well as in medicine. Our aim was to investigate the potential renoprotective effects of humic acid in a renal ischemia reperfusion model. Twenty-one rats were randomly divided into three equal groups. Intraperitoneal serum or humic acid was injected at 1, 12, and 24 h. Non-ischemic group I was evaluated as sham. The left renal artery was clamped in serum (group II) and intraperitoneal humic acid (group III) to subject to left renal ischemic reperfusion procedure. Ischemia and reperfusion time was 60 min for each. Total antioxidant status, total oxidative status, oxidative stress index, and ischemia-modified albumin levels were analyzed biochemically from the serum samples. Kidneys were evaluated histopatologically and immunohistochemically. Biochemical results showed that total oxidative status, ischemia-modified albumin, and oxidative stress index levels were significantly decreased, but total antioxidant status was increased in the humic acid group (III) compared with the ischemia group (II) On histopathological examination, renal tubular dilatation, tubular cell damage and necrosis, dilatation of Bowman's capsule, hyaline casts, and tubular cell spillage were decreased in the humic acid group (III) compared with the ischemia group (II). Immunohistochemical results showed that apoptosis was deteriorated in group III. Renal ischemia reperfusion injury was attenuated by humic acid administration. These observations indicate that humic acid may have a potential therapeutic effect on renal ischemia reperfusion injury by preventing oxidative stress.

Comparison of Intraabdominal and Trocar Site Local Anaesthetic Infiltration on Postoperative Analgesia After Laparoscopic Cholecystectomy.

PubMed

Altuntaş, Gülsüm; Akkaya, Ömer Taylan; Özkan, Derya; Sayın, Mehmet Murat; Balas, Şener; Özlü, Elif

2016-12-01

This study aimed to compare the efficacy of local anaesthetic infiltration to trocar wounds and intraperitoneally on postoperative pain as a part of a multimodal analgesia method after laparoscopic cholecystectomies. The study was performed on 90 ASA I-III patients aged between 20 and 70 years who underwent elective laparoscopic cholecystectomy. All patients had the same general anaesthesia drug regimen. Patients were randomized into three groups by a closed envelope method: group I (n=30), trocar site local anaesthetic infiltration (20 mL of 0.5% bupivacaine); group II (n=30), intraperitoneal local anaesthetic instillation (20 mL of 0.5%) and group III (n=30), saline infiltration both trocar sites and intraperitoneally. Postoperative i.v. patient controlled analgesia was initiated for 24 h. In total, 4 mg of i.v. ondansetron was administered to all patients. Visual analogue scale (VAS), nausea and vomiting and shoulder pain were evaluated at 1., 2., 4., 8., 12., 24. hours. An i.v. nonsteroidal anti-inflammatory drug (NSAID) (50 mg of dexketoprofen) as a rescue analgesic was given if the VAS was ≥5. There were no statistical significant differences between the clinical and demographic properties among the three groups (p≥0.005). During all periods, VAS in group I was significantly lower than that in groups II and III (p<0.001). Among the groups, although there was no significant difference in nausea and vomiting (p=0.058), there was a significant difference in shoulder pain. Group III (p<0.05) had more frequent shoulder pain than groups I and II. The total morphine consumption was higher in groups II and III (p<0.001 vs p<0.001) than in group I. The requirement for a rescue analgesic was significantly higher in group III (p<0.05). Trocar site local anaesthetic infiltration is more effective for postoperative analgesia, easier to apply and safer than other analgesia methods. Morphine consumption is lesser and side effects are fewer; therefore, this method can be used as a part of common practice.

Improved outcome in pediatric relapsed acute myeloid leukemia: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group.

PubMed

Kaspers, Gertjan J L; Zimmermann, Martin; Reinhardt, Dirk; Gibson, Brenda E S; Tamminga, Rienk Y J; Aleinikova, Olga; Armendariz, Hortensia; Dworzak, Michael; Ha, Shau-Yin; Hasle, Henrik; Hovi, Liisa; Maschan, Alexei; Bertrand, Yves; Leverger, Guy G; Razzouk, Bassem I; Rizzari, Carmelo; Smisek, Petr; Smith, Owen; Stark, Batia; Creutzig, Ursula

2013-02-10

In pediatric relapsed acute myeloid leukemia (AML), optimal reinduction therapy is unknown. Studies suggest that liposomal daunorubicin (DNX; DaunoXome; Galen, Craigavon, United Kingdom) is effective and less cardiotoxic, which is important in this setting. These considerations led to a randomized phase III study by the International Berlin-Frankfurt-Münster Study Group. Patients with relapsed or primary refractory non-French-American-British type M3 AML who were younger than 21 years of age were eligible. Patients were randomly assigned to fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) or to FLAG plus DNX in the first reinduction course. The primary end point was status of the bone marrow (BM) sampled shortly before the second course of chemotherapy (the day 28 BM). Data are presented according to intention-to-treat for all 394 randomly assigned patients (median follow-up, 4.0 years). The complete remission (CR) rate was 64%, and the 4-year probability of survival (pOS) was 38% (SE, 3%). The day 28 BM status (available in 359 patients) was good (≤ 20% leukemic blasts) in 80% of patients randomly assigned to FLAG/DNX and 70% for patients randomly assigned to FLAG (P = .04). Concerning secondary end points, the CR rate was 69% with FLAG/DNX and 59% with FLAG (P = .07), but overall survival was similar. However, core-binding factor (CBF) AML treated with FLAG/DNX resulted in pOS of 82% versus 58% with FLAG (P = .04). Grade 3 to 4 toxicity was essentially similar in both groups. DNX added to FLAG improves early treatment response in pediatric relapsed AML. Overall long-term survival was similar, but CBF-AML showed an improved survival with FLAG/DNX. International collaboration proved feasible and resulted in the best outcome for pediatric relapsed AML reported thus far.

A Mixed-Methods, Randomized, Controlled Feasibility Trial to Inform the Design of a Phase III Trial to Test the Effect of the Handheld Fan on Physical Activity and Carer Anxiety in Patients With Refractory Breathlessness.

PubMed

Johnson, Miriam J; Booth, Sara; Currow, David C; Lam, Lawrence T; Phillips, Jane L

2016-05-01

The handheld fan is an inexpensive and safe way to provide facial airflow, which may reduce the sensation of chronic refractory breathlessness, a frequently encountered symptom. To test the feasibility of developing an adequately powered, multicenter, multinational randomized controlled trial comparing the efficacy of a handheld fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions, measuring recruitment rates; data quality; and potential primary outcome measures. This was a Phase II, multisite, international, parallel, nonblinded, mixed-methods randomized controlled trial. Participants were centrally randomized to fan or control. All received breathlessness self-management/exercise advice and were followed up weekly for four weeks. Participants/carers were invited to participate in a semistructured interview at the study's conclusion. Ninety-seven people were screened, 49 randomized (mean age 68 years; 49% men), and 43 completed the study. Site recruitment varied from 0.25 to 3.3/month and screening:randomization from 1.1:1 to 8.5:1. There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale (two-thirds of data missing). No harms were observed. Three interview themes included 1) a fan is a helpful self-management strategy, 2) a fan aids recovery, and 3) a symptom control trial was welcome. A definitive, multisite trial to study the use of the handheld fan as part of self-management of chronic refractory breathlessness is feasible. Participants found the fan useful. However, the value of information for changing practice or policy is unlikely to justify the expense of such a trial, given perceived benefits, the minimal costs, and an absence of harms demonstrated in this study. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

The effect of intraurethral dexpanthenol on healing and fibrosis in rats with experimentally induced urethral trauma.

PubMed

Yardimci, Ibrahim; Karakan, Tolga; Resorlu, Berkan; Doluoglu, Omer Gokhan; Ozcan, Serkan; Aydın, Arif; Demirbas, Arif; Unverdi, Hatice; Eroglu, Muzaffer

2015-01-01

To determine the efficacy of dexpanthenol applied early after urethral trauma for preventing inflammation and spongiofibrosis. Twenty-seven rats were randomized and divided into 3 groups, with 9 rats in each group. The urethras of all rats were traumatized with a pediatric urethrotome knife at 6-o' clock. For 14 days, group I was given 0.9% saline twice a day (control group), group II was given dexpanthenol 500 mg/kg ampules once a day and 0.9% saline once a day, and group III was given dexpanthenol 500 mg/kg ampules twice a day intraurethrally using a 22 ga catheter sheath. On day 15, the penises of the rats were degloved to perform penectomy. The mean fibrosis scores were 2.4, 2.2, and 1.4, and mean inflammation scar scores were 2, 1.4, and 1.3 in groups I, II, and III, respectively. There was a significant difference between groups I and II for inflammation (P = .011); however, the difference for fibrosis was not significant (P = .331). The differences between groups I and III were statistically significantly different both for inflammation and fibrosis (P = .004 and P = .003, respectively). Groups II and III were not different significantly for inflammation (P = .638); however, there was less fibrosis in group III, in which high-dose dexpanthenol was administered. We showed that dexpanthenol applied early after urethral trauma significantly decreased inflammation and spongiofibrosis. We hope that our study will help to decrease strictures after urethral trauma and contribute to pharmaceutical investigations aiming to improve the success of the surgery for urethral strictures. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

PubMed

Hacker, Mallory L; DeLong, Mahlon R; Turchan, Maxim; Heusinkveld, Lauren E; Ostrem, Jill L; Molinari, Anna L; Currie, Amanda D; Konrad, Peter E; Davis, Thomas L; Phibbs, Fenna T; Hedera, Peter; Cannard, Kevin R; Drye, Lea T; Sternberg, Alice L; Shade, David M; Tonascia, James; Charles, David

2018-06-29

To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT ( p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy ( p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT ( p = 0.001). These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor. © 2018 American Academy of Neurology.

Exterior egg quality as affected by enrichment resources layout in furnished laying-hen cages.

PubMed

Li, Xiang; Chen, Donghua; Meng, Fanyu; Su, Yingying; Wang, Lisha; Zhang, Runxiang; Li, Jianhong; Bao, Jun

2017-10-01

This study aimed to investigate the effects of enrichment resources (a perch, dustbath, and nest) layout in furnished laying-hen cages (FC) on exterior quality of eggs. One hundred and sixty-eight (168) Hy-Line Brown laying hens at 16 weeks of age were randomly distributed to four treatments: small furnished cages (SFC), medium furnished cages type I (MFC-I), medium furnished cages type II (MFC-II), and medium furnished cages type III (MFC-III). Each treatment had 4 replicates or cages with 6 hens for SFC (24 birds for each SFC) and 12 hen/cage for MFC-I, -II, and -III (48 birds for each MFC-I, -II and -III). Following a 2-week acclimation, data collection started at 18 weeks of age and continued till 52 weeks of age. Dirtiness of egg surface or cracked shell as indicators of the exterior egg quality were recorded each week. The results showed that the proportion of cracked or dirty eggs was significantly affected by the FC type (p<0.01) in that the highest proportion of cracked or dirty eggs was found in MFC-I and the lowest proportion of dirty eggs in SFC. The results of this showed that furnished cage types affected both dirty eggs and cracked eggs (p<0.01). The results also indicated that not nest but dustbath lead to more dirty eggs. Only MFC-I had higher dirty eggs at nest than other FC (p< 0.01). The results of dirty eggs in MFC-I and MFC-II compared with SFC and MFC-III seemed suggest that a low position of dustbath led to more dirty eggs. SFC design affected exterior egg quality and the low position of dustbath in FC resulted in higher proportion of dirty eggs.

Results of surgery on 6589 gastric cancer patients and immunochemosurgery as the best treatment of advanced gastric cancer.

PubMed Central

Kim, J P; Kwon, O J; Oh, S T; Yang, H K

1992-01-01

Results of 6589 gastric cancer operations at the Department of Surgery, Seoul National University Hospital, from 1970 to 1990 were reported. About two thirds (76.6%) were advanced gastric cancer (stages III and IV). The 5-year survival rate of operated stage III gastric cancer was only 30.6%, with frequent recurrence. Conversely, cell-mediated immunities of advanced gastric cancer patients were significantly decreased. Therefore, to improve the cure rate and to prevent or delay recurrence, curative surgery with confirmation of free resection margins and systematic lymph node dissection of perigastric vessels were performed and followed by early postoperative immunotherapy and chemotherapy (immunochemosurgery) in stage III patients. To evaluate the effect of immunochemosurgery, two randomized trials were studied in 1976 and 1981. In first trial, 5-fluorouracil, mitomycin C, and cytosine arabinoside for chemotherapy and OK 432 for immunotherapy were used. The 5-year survival rates for surgery alone (n = 64) and immunochemosurgery (n = 73) were 23.4% and 44.6%, respectively, a significant difference. In the second trial, there were three groups: group I, immunochemosurgery (n = 159); group II, surgery and chemotherapy (n = 77); and group III, surgery alone (n = 94). 5-Fluorouracil and mitomycin C for chemotherapy and OK-432 for immunotherapy were administered for 2 years. The 5-year survival rate of group I was 45.3%, significantly higher than the 29.8% of group II and than the 24.4% of group III. The postoperative 1-chloro-2.4-dinitrobenzene test, T-lymphocyte percentage, phytohemagglutinin- and con-A-stimulated lymphoblastogenesis and the antibody-dependent cell-mediated cytotoxicity test showed more favorable values in the immunochemosurgery group. Therefore, immunochemosurgery is the best multimodality treatment for advanced gastric cancer. PMID:1417176

Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

PubMed

Zhang, Sheng; Liang, Fei; Li, Wenfeng

2017-11-01

The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

Periodontal soft tissue root coverage procedures: a systematic review from the AAP Regeneration Workshop.

PubMed

Chambrone, Leandro; Tatakis, Dimitris N

2015-02-01

This paper aims to create a "bridge" between research and practice by developing a practical, extensive, and clinically relevant study that translates evidence-based findings on soft tissue root coverage (RC) of recession-type defects to daily clinical practice. This review is prepared in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement based on the proposed focused questions. A literature search with no restrictions regarding status or the language of publication was performed for MEDLINE and EMBASE databases up to and including June 2013. Systematic reviews (SRs), randomized clinical trials, controlled clinical trials, case series, and case reports evaluating recession areas that were treated by means of RC procedures were considered eligible for inclusion through the three parts of the study (part I, an overview of the base of SRs; part II, an alternative random-effects meta-analyses on mean percentage of RC and sites exhibiting complete RC; and part III, an SR of non-randomized trials exploring other conditions not extensively evaluated by previous SRs). Data on Class I, II, III, and IV recessions, type of histologic attachment achieved with treatment, recipient- and donor-site anatomic characteristics, smoking-related outcomes, root surface conditions, tooth type and location, long-term effectiveness outcomes, unusual conditions that may be reported during conventional daily practice, and patient-centered outcomes were assessed as well. Of the 2,456 potentially eligible trials, 234 were included. Data on Class I, II, III, and IV gingival recessions, histologic attachment achieved after treatment, recipient- and donor-site anatomic characteristics, smoking-related outcomes, root surface conditions/biomodification, tooth type and location, long-term effectiveness outcomes and unusual conditions that may be reported during conventional daily practice, and patient-centered outcomes (i.e., esthetic, visual analog scale, complications, hypersensitivity, patients perceptions) were assessed. Subepithelial connective tissue (CT)-based procedures and coronally advanced flap plus acellular dermal matrix grafts, enamel matrix derivative, or collagen matrix led to the best improvements of recession depth, clinical attachment level (CAL) gain, and keratinized tissue (KT). Some conditions, such as smoking and use of magnification, may affect RC outcomes. All RC procedures can provide significant reduction in recession depth and CAL gain for Miller Class I and II recession-type defects. Subepithelial CT graft-based procedures provided the best outcomes for clinical practice because of their superior percentages of mean and complete RC, as well as significant increase of KT.

Genetic relatedness between oral and intestinal isolates of Porphyromonas endodontalis by analysis of random amplified polymorphic DNA.

PubMed

Gonçalves, R B; Väisänen, M L; Van Steenbergen, T J; Sundqvist, G; Mouton, C

1999-01-01

Genomic fingerprints from the DNA of 27 strains of Porphyromonas endodontalis from diverse clinical and geographic origins were generated as random amplified polymorphic DNA (RAPD) using the technique of PCR amplification with a single primer of arbitrary sequence. Cluster analysis of the combined RAPD data obtained with three selected 9- or 10-mer-long primers identified 25 distinct RAPD types which clustered as three main groups identifying three genogroups. Genogroups I and II included exclusively P. endodontalis isolates of oral origin, while 7/9 human intestinal strains of genogroup III which linked at a similarity level of 52% constituted the most homogeneous group in our study. Genotypic diversity within P. endodontalis, as shown by RAPD analysis, suggests that the taxon is composed of two oral genogroups and one intestinal genogroup. This hypothesis remains to be confirmed.

An international randomized study of a home-based self-management program for severe COPD: the COMET.

PubMed

Bourbeau, Jean; Casan, Pere; Tognella, Silvia; Haidl, Peter; Texereau, Joëlle B; Kessler, Romain

2016-01-01

Most hospitalizations and costs related to COPD are due to exacerbations and insufficient disease management. The COPD patient Management European Trial (COMET) is investigating a home-based multicomponent COPD self-management program designed to reduce exacerbations and hospital admissions. Multicenter parallel randomized controlled, open-label superiority trial. Thirty-three hospitals in four European countries. A total of 345 patients with Global initiative for chronic Obstructive Lung Disease III/IV COPD. The program includes extensive patient coaching by health care professionals to improve self-management (eg, develop skills to better manage their disease), an e-health platform for reporting frequent health status updates, rapid intervention when necessary, and oxygen therapy monitoring. Comparator is the usual management as per the center's routine practice. Yearly number of hospital days for acute care, exacerbation number, quality of life, deaths, and costs.

Role of Aspirin in Breast Cancer Survival.

PubMed

Chen, Wendy Y; Holmes, Michelle D

2017-07-01

Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer. Although the potential mechanism for aspirin preventing breast cancer is not known, possible pathways may involve platelets, inflammation, cyclooxygenase (COX) 2, hormones, or PI3 kinase. This review article summarizes the current epidemiologic and clinical trial evidence as well as possible underlying mechanisms that justify current phase III randomized trials of aspirin to improve breast cancer survival.

Manganese exposure: neuropsychological and neurological symptoms and effects in welders.

PubMed

Bowler, Rosemarie M; Gysens, Sabine; Diamond, Emily; Nakagawa, Sanae; Drezgic, Marija; Roels, Harry A

2006-05-01

Manganese exposure reportedly may have an adverse effect on CNS function and mood. Sixty-two welders with clinical histories of exposure to manganese were compared to 46 matched regional controls chosen at random from a telephone directory. The following tests were given: Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Memory Scale (WMS-III), Boston Naming, WRAT-3, Cancellation H, Trail Making Tests A and B, Auditory Consonant Trigrams, Stroop, Rey-Osterreith, Animal Naming, Controlled Oral Word Association (COWAT), Test of Memory Malingering, Rey 15-item, Fingertapping, Grooved Pegboard, Dynamometer, Visual Attention Test, Lanthony d-15 Color Vision, Vistech Contrast Sensitivity, and Schirmer strips. The controls were administered a shorter battery of tests and the Rey-Osterreith, Animal Naming and some of the subtests of the WAIS-III, WMS-III were not administered. Mood tests, given to both groups, included the Symptom Checklist-40, Symptom Checklist-90-R, Profile of Mood Scale, Beck Depression Inventory II, and Beck Anxiety Inventory. Forty-seven welders and 42 controls were retained for statistical analysis after appropriate exclusions. Results showed a high rate of symptom prevalence and pronounced deficits in motor skills, visuomotor tracking speed and information processing, working memory, verbal skills (COWAT), delayed memory, and visuospatial skills. Neurological examinations compared to neuropsychological test results suggest that neuropsychologists obtain significantly more mood symptoms overall. Odds ratios indicate highly elevated risk for neuropsychological and neurological symptomatology of manganism. Mood disturbances including anxiety, depression, confusion, and impaired vision showed very high odds ratios. Neurological exams and neuropsychological tests exhibit complementarity and differences, though neuropsychological methods may be more sensitive in detecting early signs of manganism. The present study corroborates the findings of our previous study in another group of welders.

Differential effects of deep brain stimulation target on motor subtypes in Parkinson's disease.

PubMed

Katz, Maya; Luciano, Marta San; Carlson, Kimberly; Luo, Ping; Marks, William J; Larson, Paul S; Starr, Philip A; Follett, Kenneth A; Weaver, Frances M; Stern, Matthew B; Reda, Domenic J; Ostrem, Jill L

2015-04-01

The Veterans Administration Cooperative Studies Program #468, a multicenter study that randomized Parkinson's disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this data set to evaluate whether PD motor subtypes responded differently to the 2 stimulation targets. We classified 235 subjects by motor subtype: tremor dominant (TD), intermediate (I), or postural instability gait difficulty (PIGD), based on pre-DBS baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores off-medication. The primary outcome was change in UPDRS part III (UPDRS-III) off-medication scores from baseline to 24 months post-DBS, compared among subjects with particular PD motor subtypes and by DBS target (STN vs GPi). Changes in tremor, rigidity, akinesia, and gait scores were also assessed using the UPDRS. TD patients had greater mean overall motor improvement, measured by UPDRS-III, after GPi DBS, compared to STN DBS (17.5 ± 13.0 vs 14.6 ± 14.9, p = 0.02), with improvement in gait accounting for this difference. Regardless of stimulation target, PIGD subjects had lower mean overall improvement in UPDRS-III scores compared with I or TD subjects (8.7 ± 12.2 vs 21.7 ± 11.2 vs 16.3 ± 13.8, p = 0.001). Our results suggest that responsiveness to both GPi and STN DBS is similar among different PD motor subtypes, although the TD motor subtype may have a greater response to GPi DBS with respect to gait. PIGD patients obtained less overall benefit from stimulation. © 2015 American Neurological Association.

Cohesion among nurses: a comparison of bedside vs. charge nurses' perceptions in Australian hospitals.

PubMed

Chaboyer, W; Najman, J; Dunn, S

2001-08-01

This study examines the extent to which hospital nurses view their working environment in a positive sense, working as a cohesive group. Despite the fact that nursing in Australia is now considered a profession, it has been claimed that nurses are an oppressed group who use horizontal violence, bullying and aggression in their interactions with one and other. After ethical approval, a random sample of 666 nurses working directly with patients and all 333 critical care nurses employed in three large tertiary Australian hospitals were invited to participate in the study in the late 1990s. A mailed survey examined the perceptions of interaction nurses had with each other. The hypothesis, that level of employment (either Level I bedside nurses or Level II/III clinical leaders) and area of work (either critical care or noncritical care) would influence perceptions of cohesion, as measured by the cohesion amongst nurses scale (CANS) was tested. In total 555 (56%) surveys were returned. Of these, 413 were returned by Level I and 142 by Level II/III nurses. Of this sample, 189 were critical care and 355 noncritical care nurses. There was no difference between Level I and II/III nurses in mean CANS scores. It is interesting to note that the item rated most positively was "nurses on the units worked well together", however, the item rated least positive was "staff can be really bitchy towards each other" for both Level I and II/III nurses. There was no difference in CANS scores between critical care and noncritical care nurses. Nurses working in Australian hospitals perceived themselves to be moderately cohesive but, as would be expected in other work settings, some negative perceptions existed.

Risk prediction for chronic kidney disease progression using heterogeneous electronic health record data and time series analysis.

PubMed

Perotte, Adler; Ranganath, Rajesh; Hirsch, Jamie S; Blei, David; Elhadad, Noémie

2015-07-01

As adoption of electronic health records continues to increase, there is an opportunity to incorporate clinical documentation as well as laboratory values and demographics into risk prediction modeling. The authors develop a risk prediction model for chronic kidney disease (CKD) progression from stage III to stage IV that includes longitudinal data and features drawn from clinical documentation. The study cohort consisted of 2908 primary-care clinic patients who had at least three visits prior to January 1, 2013 and developed CKD stage III during their documented history. Development and validation cohorts were randomly selected from this cohort and the study datasets included longitudinal inpatient and outpatient data from these populations. Time series analysis (Kalman filter) and survival analysis (Cox proportional hazards) were combined to produce a range of risk models. These models were evaluated using concordance, a discriminatory statistic. A risk model incorporating longitudinal data on clinical documentation and laboratory test results (concordance 0.849) predicts progression from state III CKD to stage IV CKD more accurately when compared to a similar model without laboratory test results (concordance 0.733, P<.001), a model that only considers the most recent laboratory test results (concordance 0.819, P < .031) and a model based on estimated glomerular filtration rate (concordance 0.779, P < .001). A risk prediction model that takes longitudinal laboratory test results and clinical documentation into consideration can predict CKD progression from stage III to stage IV more accurately than three models that do not take all of these variables into consideration. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Pain Elimination during Injection with Newer Electronic Devices: A Comparative Evaluation in Children

PubMed Central

Saha, Sonali; Jaiswal, JN; Samadi, Firoza

2014-01-01

ABSTRACT Aim: The present study was taken up to clinically evaluate and compare effectiveness of transcutaneous electrical nerve stimulator (TENS) and comfort control syringe (CCS) in various pediatric dental procedures as an alternative to the conventional method of local anesthesia (LA) administration. Materials and methods: Ninety healthy children having at least one deciduous molar tooth indicated for extraction in either maxillary right or left quadrant in age group of 6 to 10 years were randomly divided into three equal groups having 30 subjects each. Group I: LA administration using conventional syringe, group II: LA administration using TENS along with the conventional syringe, group III: LA administration using CCS. After LA by the three techniques, pain, anxiety and heart rate were measured. Statistical analysis: The observations, thus, obtained were subjected to statistical analysis using analysis of variance (ANOVA), student t-test and paired t-test. Results: The mean pain score was maximum in group I followed by group II, while group III revealed the minimum pain, where LA was administered using CCS. Mean anxiety score was maximum in group I followed by group II, while group III revealed the minimum score. Mean heart rate was maximum in group I followed in descending order by groups II and III. Conclusion: The study supports the belief that CCS could be a viable alternative in comparison to the other two methods of LA delivery in children. How to cite this article: Bansal N, Saha S, Jaiswal JN, Samadi F. Pain Elimination during Injection with Newer Electronic Devices: A Comparative Evaluation in Children. Int J Clin Pediatr Dent 2014;7(2):71-76. PMID:25356003

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study.

PubMed

Sethi, Rakesh; Naqash, Imtiaz A; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only.

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study

PubMed Central

Sethi, Rakesh; Naqash, Imtiaz A.; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

Background and Aim: The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Materials and Methods: Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Results: Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Conclusion: Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only. PMID:27057213

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basu, Partha, E-mail: BasuP@iarc.fr; Jenson, Alfred Bennett; Majhi, Tapas

Purpose: Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies, we designed this randomized phase 2 open-label trial to assess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiation therapy (IFN-RA-radiation) to treat stage III cervical cancer. Methods and Materials: Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation therapy; study arm patients received IFN (3 × 10{sup 6} IU subcutaneously) 3 times a week for 4 weeks and dailymore » RA (40 mg orally) for 30 days starting on day 1 of radiation, whereas control arm patients received weekly cisplatinum (40 mg/m{sup 2}) for 5 weeks during radiation. Patients were followed for 3 years. The primary endpoint was overall survival at 3 years. Results: Patients in the study (n=104) and control (n=105) groups were comparable for clinicopathological characteristics, radiation therapy–related variables and treatment response. Proportions of disease-free patients in the study and control groups were 38.5% and 44.8%, respectively, after median follow-up of 29.2 months. Hazard ratios were 0.67 (95% confidence interval [CI]: 0.44-1.01) and 0.69 (95% CI: 0.44-1.06) for overall and disease-fee survival, respectively, comparing the study group to control, and demonstrated an inferior outcome with RA-IFN-radiation, although differences were statistically nonsignificant. Kaplan-Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to those in the control. Acute toxicities of chemoradiation were significantly higher with 2 acute toxicity-related deaths. Conclusions: Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemoradiation despite being less toxic. The trends predicted an inferior outcome with the RA-IFN combination.« less

Pilates

PubMed Central

Di Lorenzo, Christine E.

2011-01-01

Context: The interest and popularity of Pilates is increasing worldwide. In addition to being used in fitness programs, it is being used in some rehabilitation programs. Evidence Acquisition: This review summarizes level III evidence from 1995 to 2009 obtained from PubMed (MEDLINE), CINAHL, and the Internet. Meta-analyses, systematic reviews, randomized controlled trials, and controlled trials published in peer-reviewed journals were retrieved for appraisal. The keywords searched were Pilates and core stabilization. Results: Ninety articles were identified in MEDLINE and CINAHL; 9 articles satisfied the inclusion criteria for level III evidence. Conclusion: There is a scientific basis for the effectiveness of Pilates exercise, with limited evidence to support it as a rehabilitative intervention. PMID:23016028

Bell experiments with random destination sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sciarrino, Fabio; Mataloni, Paolo; Istituto Nazionale di Ottica, Consiglio Nazionale delle Ricerche

2011-03-15

It is generally assumed that sources randomly sending two particles to one or two different observers, random destination sources (RDSs), cannot be used for genuine quantum nonlocality tests because of the postselection loophole. We demonstrate that Bell experiments not affected by the postselection loophole may be performed with (i) an RDS and local postselection using perfect detectors, (ii) an RDS, local postselection, and fair sampling assumption with any detection efficiency, and (iii) an RDS and a threshold detection efficiency required to avoid the detection loophole. These results allow the adoption of RDS setups which are simpler and more efficient formore » long-distance free-space Bell tests, and extend the range of physical systems which can be used for loophole-free Bell tests.« less

Effectiveness of Antimicrobial Therapy after Extraction of Impacted Mandibular Third Molar: A Randomized Clinical Trial.

PubMed

Rabi, A; Maheshwari, Rahul; Srinivasan, Bhuvaneshwari; Warad, Lata P; Suvarna, C C; Tank, Kartik S

2018-01-01

The present study was conducted with the aim of evaluating the effectiveness of antimicrobial therapy following extraction of an impacted mandibular third molar. This randomized controlled trial was conducted on a total of 60 patients who were randomly assigned into three groups: Group I individuals were given 625 mg of combined amoxicillin and clavulanic acid tablet; 625 mg of combined amoxicillin and clavulanic acid tablet + 400 mg metronidazole tablet was given to group II individuals; whereas group III individuals were assigned no treatment. All the individuals underwent surgical extraction of impacted mandibular third molars under strict aseptic techniques, with minimal trauma to the surrounding tissues. Mouth opening in millimeters was recorded postoperatively using Vernier calipers on the 1st, 3rd, 5th, and 7th days. A 4-point visual analog scale (VAS) was used for assessing postoperative pain. Patient satisfaction was further assessed in a subjective manner using a graded scale from "very satisfied" to "very unsatisfied". The present study included individuals between the ages of 20 and 35 years. Group II individuals showed slightly better satisfaction than the other group individuals. There was no statistically significant difference between the mean age of groups. It was observed that on day 3, the number of individuals with severe pain was slightly reduced in the group I compared with group III individuals. On day 5, participants with no pain were significantly more in group II followed by group I. Furthermore, there was a statistically significant difference between the study groups with respect to mouth opening on days 3 and 5. It was concluded from this trial that the administration of postoperative antimicrobials showed no significant differences in the degree of postoperative complications that occur following the surgical extraction of impacted mandibular third molars. Antimicrobial drugs are routinely used to reduce the chances of surgical site infection, either preopera-tively or postoperatively. Therefore, the clinicians should have sound knowledge about choosing the better antimicrobial drug after the extraction of impacted third molars.